Use of poria cocos or extract thereof in the preparation of a drug for preventing or reducing peritoneal metastasis of gastric cancer

Abstract

This invention discloses the application of Poria cocos or its extracts in the preparation of drugs for preventing peritoneal metastasis of gastric cancer, belonging to the field of pharmaceutical technology. This invention, through in vivo pharmacodynamic experiments, is the first to demonstrate that the aqueous extract of Poria cocos can inhibit peritoneal metastasis of gastric cancer by upregulating Fem1b, with effects comparable to chemotherapy drugs. Mechanism of action studies show that Poria cocos or its extracts exert a preventive effect by upregulating the expression of a series of tumor suppressor genes such as Fem1b, Ifi202, and Dmbt1. Compared with existing invasive preventive methods (such as intraperitoneal chemotherapy), the oral Poria cocos or its extract regimen provided by this invention has significant advantages such as safety, low toxicity, non-invasiveness, high patient compliance, and low cost, providing a novel strategy and drug option for preventing peritoneal metastasis of gastric cancer.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to new pharmaceutical uses of the traditional Chinese medicine Poria cocos or its extracts, particularly in the preparation of drugs for preventing peritoneal metastasis of gastric cancer. Background Technology

[0002] Gastric cancer is a highly prevalent malignant tumor of the digestive system worldwide, consistently ranking among the leading causes of death from malignant tumors. Peritoneal metastasis is one of the most common forms of distant metastasis in the progression of gastric cancer. It refers to the detachment of gastric cancer cells originating from the gastric mucosal epithelium from the primary lesion, where they implant and grow on the surface of the parietal peritoneum, visceral peritoneum, and greater omentum, forming metastatic nodules or disseminated lesions. This is a significant reason for poor prognosis and significantly shortened survival in gastric cancer patients. Clinical data shows that once peritoneal metastasis occurs in gastric cancer, patients often lose the opportunity for radical surgery and have low sensitivity to conventional chemotherapy and targeted therapy, resulting in poor quality of life and extremely difficult clinical treatment. Therefore, safe, effective, and accessible strategies for preventing peritoneal metastasis in gastric cancer have become a critical issue urgently needing to be addressed in the clinical diagnosis and treatment and basic research of gastric cancer.

[0003] Currently, clinical methods for preventing peritoneal metastasis of gastric cancer are mainly divided into two categories: surgical tumor-free techniques and prophylactic intraperitoneal chemotherapy (mainly HIPEC / NIPEC). Both have significant limitations in clinical application and are difficult to meet the ideal prevention needs.

[0004] I. Limitations of Surgical Tumor-Free Techniques Surgical tumor-free techniques are a core operational standard for preventing iatrogenic tumor dissemination during radical gastrectomy for gastric cancer. The core objective is to reduce intraoperative iatrogenic tumor cell shedding and implantation through procedures such as avoiding tumor compression, properly covering the tumor wound, and thoroughly irrigating the abdominal cavity. However, this technique has the following drawbacks: Inconsistent implementation standards and insufficient adoption and quality control: Globally and domestically, there are no unified, quantifiable operational guidelines. Significant differences in operational skills and implementation efforts among different medical institutions and surgeons lead to inconsistent preventative effects. Furthermore, the definition of key indications such as "large-scale tumor invasion of the serosal region" is ambiguous. With the increasing prevalence of laparoscopic minimally invasive surgery, clinicians are prone to inappropriately broadening surgical indications, increasing the risk of tumor cell atomization and dissemination caused by pneumoperitoneum and instrument manipulation.

[0005] It cannot eliminate pre-existing subclinical micrometastases: Surgical tumor-free techniques can only intervene in tumor cells that are mechanically disseminated during surgery. They have no effect on eliminating peritoneal micrometastases that are present before or during surgery and cannot be detected by imaging (especially those with positive peritoneal exfoliative cytology but no visible metastatic lesions), thus creating a clear blind spot in prevention.

[0006] II. Limitations of Prophylactic Intraperitoneal Chemotherapy (HIPEC / NIPEC) Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic intraperitoneal chemotherapy (NIPEC) are local adjuvant prophylactic methods used in recent years for high-risk gastric cancer patients. These methods involve directly administering chemotherapy drugs into the peritoneum to kill free tumor cells. However, these techniques have significant drawbacks: The evidence for clinical benefit is inconsistent, and it is difficult to accurately define the beneficiary population: Most existing studies are small-scale, single-center retrospective studies with significant discrepancies in conclusions. Some studies show survival benefits, while others do not observe significant differences. It is impossible to clearly define the beneficiary population under stratified indicators such as TNM stage, serous lesion area, and Lauren classification, resulting in a lack of precise guidance for clinical application.

[0007] The treatment is highly invasive, significantly increasing complications and risks: HIPEC requires 60–90 minutes of perfusion before and after abdominal closure, significantly prolonging the operation and anesthesia time; chemotherapy drugs (mitomycin C, cisplatin, etc.) are prone to causing chemical complications such as bone marrow suppression, liver and kidney damage, intestinal mucositis, and abdominal adhesions, while increasing the risks of anastomotic leakage, bleeding, and abdominal infection. The adverse effects of high-temperature perfusion on intestinal blood supply and anastomotic healing are also major concerns in surgical clinics.

[0008] High technical barriers, high consumption of medical resources, and poor accessibility: HIPEC requires specialized hyperthermic perfusion therapy equipment, a multidisciplinary collaborative team (surgery, anesthesia, nursing, pharmacy) and standardized operating procedures, and can only be carried out in large oncology centers, making it difficult to popularize in primary hospitals; at the same time, the equipment, consumables, drugs and hospitalization time significantly increase treatment costs, resulting in poor health economic benefits.

[0009] Treatment timing and options are limited: prophylactic intraperitoneal chemotherapy can only be performed during or shortly after surgery, with a narrow treatment window, making it impossible to achieve preoperative prevention or long-term postoperative maintenance intervention; although NIPEC is easy to operate, its drug tissue penetration and tumor killing efficacy are significantly lower than HIPEC, and core protocols such as optimal drugs, timing of administration, and course of treatment have not yet been established.

[0010] In summary, existing technologies for preventing peritoneal metastasis of gastric cancer have many problems, such as high invasiveness, high toxicity, unclear benefits, low accessibility, and limited application scenarios. Clinically, there is an urgent need for a new prevention strategy that is non-invasive, low in toxicity, convenient to administer, applicable throughout the entire course of treatment, and suitable for widespread promotion, in order to fill the current technological gap and improve the prognosis of gastric cancer patients. Summary of the Invention

[0011] This invention aims to address the technical problems of existing gastric cancer peritoneal metastasis prevention programs, which are characterized by high toxicity, invasiveness, poor patient compliance, and high demands on medical resources. This invention provides an oral preventative program based on the natural drug Poria cocos or its extracts. This program is safe, low in toxicity, non-invasive, and has a definite therapeutic effect.

[0012] To achieve the above objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides the use of Poria cocos and its extracts in the preparation of a medicament for preventing peritoneal metastasis of gastric cancer.

[0013] Preferably, the drug is administered orally.

[0014] Preferably, the Poria cocos is the dried sclerotium of the fungus Poriacocos (Schw.) Wolf, belonging to the Polyporaceae family.

[0015] Preferably, the dosage of the drug, calculated based on raw Poria cocos, is 1-20 g / kg body weight per day.

[0016] Preferably, the dosage of the drug, calculated based on raw Poria cocos, is 8-12 g / kg body weight per day, and more preferably 10 g / kg body weight per day.

[0017] Preferably, the drug is used during the perioperative period of surgical resection of the primary gastric cancer lesion, including preoperative, intraoperative and / or postoperative administration.

[0018] Preferably, the Poria cocos or its extract prevents peritoneal metastasis of gastric cancer by upregulating the expression of tumor suppressor genes; the tumor suppressor genes are selected from one or more of Fem1b, Ifi202, Dmbt1, Filip1l, Myh11, Ltf, Faap100, Camp, Gmcl1, Uvssa, B9d1, Snca, Cntn3, Hspb6, Apoa2, Apoa1, Ahsg, Arhgap32, Ambp, Aldh1a1, Wdr47, Orm1, Mug1, and Gpld1.

[0019] In a second aspect, the present invention provides a pharmaceutical composition for preventing peritoneal metastasis of gastric cancer, comprising a therapeutically effective amount of Poria cocos and a pharmaceutically acceptable carrier.

[0020] Preferably, the effective dose is 10g / kg based on the amount of raw Poria cocos.

[0021] Preferably, the pharmaceutical composition is an oral preparation, such as tablets, capsules, granules, powders, or oral liquids.

[0022] Preferably, the Poria cocos is present in the pharmaceutical composition in the form of an aqueous extract or other extracts.

[0023] Beneficial effects:

[0024] Compared with the prior art, the present invention has the following significant advantages: High safety and low toxicity: As a traditional medicinal and edible herb, Poria cocos has a well-established safety profile for long-term use. Animal experiments have demonstrated that, at effective preventative doses, it exhibits no significant acute toxicity, thus avoiding serious side effects commonly associated with chemotherapy drugs, such as bone marrow suppression and liver and kidney damage.

[0025] Non-invasive and high compliance: The oral administration method eliminates the need for surgery or invasive procedures, greatly improving patient acceptance and long-term medication compliance, making it suitable for long-term maintenance prophylaxis after surgery.

[0026] Novel Mechanism of Action: This invention is the first to discover through proteomics analysis that the effect of Poria cocos in preventing peritoneal metastasis of gastric cancer is related to the upregulation of the expression of a series of tumor suppressor genes (such as Fem1b, Ifi202, Dmbt1, Filip1l, Myh11, Ltf, etc.), revealing its multi-target anti-cancer mechanism at the molecular level.

[0027] Definite efficacy: Through rigorous in vivo pharmacodynamic models (mouse models simulating the clinical progression and metastasis of gastric cancer), it has been confirmed that oral administration of Poria cocos water extract can significantly inhibit the implantation and growth of gastric cancer cells in the peritoneum. Its preventive effect is comparable to that of the positive chemotherapy drug oxaliplatin, and it is suitable for high-risk gastric cancer patients, perioperative patients, and patients with positive free cancer cells in the peritoneum.

[0028] It has low requirements for medical resources and high accessibility: it does not require expensive equipment or complicated operations, is inexpensive, and is easy to promote and apply in medical institutions at all levels, with significant health economic advantages. Attached Figure Description

[0029] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0030] Figure 1 UPLC-Q-TOF-MS / MS analysis of the total ion chromatogram and component classification diagram of the aqueous extract of Poria cocos; among which... Figure 1 A is the total ion chromatogram in positive ion mode. Figure 1 B is the total ion chromatogram in negative ion mode. Figure 1 C is a statistical diagram illustrating the classification of identified components such as organic acids, triterpenoid saponins, alkaloids, and sesquiterpenes.

[0031] Figure 2 This is a schematic diagram illustrating the effect of Poria cocos aqueous extract on the proliferation of gastric cancer tumors in vivo; among which... Figure 2 A shows in vivo bioluminescence imaging of tumors in each group of mice. Figure 2B is a bar chart showing the statistical weight of tumors in each group of mice.

[0032] Figure 3 HE-stained sections of peritoneum, intestine, and liver tissue from each group of mice (×200). Figure 3 The left side shows HE-stained sections of peritoneum, intestine, and liver tissue from mice in the model control group, the Poria cocos treatment group, and the oxaliplatin positive control group. Figure 3 The right side shows a bar chart statistically analyzing the number of metastatic nodules in the intestine.

[0033] Figure 4 These are photographs of the intestinal tract specimens of mice in each group; from top to bottom, they are the intestinal tissues of mice in the model control group, the Poria cocos treatment group, and the oxaliplatin positive control group.

[0034] Figure 5 This is a heatmap showing the differentially expressed genes in tumor tissues of mice in the Poria cocos treatment group and the model control group. Different colors in the graph represent the gene expression levels (red indicates high expression, blue indicates low expression). The horizontal axis represents the sample group, and the vertical axis represents the differentially expressed genes.

[0035] Figure 6 This is a schematic diagram illustrating the effect of Fem1b knockdown on the invasion and migration ability of gastric cancer MKN-45 cells and Fem1b protein expression; among them, Figure 6 A is a crystal violet staining image from the Transwell migration assay; Figure 6 B is an electrophoresis image of Fem1b protein expression in each group detected by Western Blot. Actin was used as an internal control to verify the knockdown efficiency of Fem1b siRNA and the regulatory effect of Poria cocos water extract on Fem1b expression.

[0036] Figure 7 The bar chart shows the statistical indices of the major organs of mice in each group: heart / body weight ratio, liver / body weight ratio, spleen / body weight ratio, lung / body weight ratio, and kidney / body weight ratio. Data are expressed as mean ± standard deviation. ns indicates no statistically significant difference compared with the model control group, and **p<0.01 indicates a highly statistically significant difference compared with the model control group. Detailed Implementation

[0037] The following embodiments further illustrate the content of the present invention, but should not be construed as limiting the present invention. Modifications or substitutions made to the methods, steps, or conditions of the present invention without departing from the spirit and substance of the invention are all within the scope of the present invention. Where specific techniques or conditions are not specified in the embodiments, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments used without specified manufacturers are all conventional products that can be purchased through legitimate channels.

[0038] Example 1: Preparation and Identification of Poria Cocos Aqueous Extract (I) Preparation process 1. Raw material processing: Weigh 400g of dried Poria cocos medicinal material (identified as the dried sclerotium of the fungus Poriacocos (Schw.) Wolf of the Polyporaceae family), add 7 times the volume of purified water and soak for 30 minutes to allow the medicinal material to fully absorb water and soften.

[0039] 2. Heating extraction: Add purified water to the soaked Poria cocos to a total volume of 4000mL, and heat at 85-90℃ for 2 hours. Stir every 30 minutes during the extraction process to promote the dissolution of active ingredients.

[0040] 3. Filtration and re-extraction: After the extract is cooled to room temperature, it is filtered through 4 layers of gauze; 2000 mL of purified water is added to the filter residue, and the extract is re-extracted for 1 hour under the same temperature conditions. The two filtrates are then combined after filtration.

[0041] 4. Concentration and volume adjustment: The combined filtrate was concentrated under reduced pressure at 50-60℃ and -0.08~-0.09MPa vacuum to about 75mL; the concentration container was washed with a small amount of purified water, and the washing liquid was added to the concentrate. The volume was adjusted to 80mL with purified water to obtain a Poria cocos water extract with a crude drug concentration of 5g / mL (each 1mL of the extract is equivalent to 5g of crude Poria cocos). The extract was stored at 4℃ for later use.

[0042] (ii) Component identification The components of the aqueous extract of Poria cocos were analyzed by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS / MS). Data acquisition conditions: electrospray ionization (ESI) source, simultaneous detection in positive and negative ion modes, mass scan range m / z 50-1500. A total of 41 major components were identified by comparison with standards and database matching. The results are shown in the figure. Figure 1 .

[0043] Depend on Figure 1 It is known that the aqueous extract of Poria cocos mainly contains various types of active substances, such as organic acids (e.g., 16-oxoporous acid A, dehydrotomonic acid, etc.), triterpenoid saponins (e.g., pachymic acid, dentinic acid, etc.), alkaloids, sesquiterpenes, and sugars, which provide the material basis for its pharmacological effects.

[0044] Example 2: In vivo pharmacodynamic evaluation of Poria cocos aqueous extract against peritoneal metastasis of gastric cancer (a) Experimental materials • Laboratory animals: SPF-grade 6-week-old Balb / c nude mice, weighing 18-22g, half male and half female, housed in an SPF-grade barrier environment at a temperature of 22±2℃ and a humidity of 50%-60%, with a 12-hour light-dark cycle, and free access to food and water.

[0045] • Cells and reagents: Human gastric cancer MKN-45-luc cells expressing luciferase; D-luciferin potassium salt (15 mg / mL, freshly prepared); tribromoethanol anesthetic (5%, stored on ice); oxaliplatin injection.

[0046] (II) Model Construction 1. Subcutaneous donor tumor preparation: MKN-45-luc cells in logarithmic growth phase were used at a rate of 1×10⁻⁶. 6 The tumors were inoculated subcutaneously on the right back of Balb / c nude mice at a density of 100 μL per mouse. When the subcutaneous tumors grew to a diameter of 0.8-1.0 cm, the tumor tissue was aseptically dissected.

[0047] 2. Orthotopic transplantation model construction: The detached tumor tissue was cut into small pieces of about 1 mm³, and one piece of tumor was surgically inoculated into the subserosal layer of the stomach of experimental mice to establish an orthotopic transplantation-spontaneous peritoneal metastasis model of gastric cancer. The mice were then fed and recovered normally after the operation.

[0048] (III) Grouping and Dosing The successfully modeled nude mice were randomly divided into 3 groups of 5 mice each: 1. Model control group (NC): Administered an equal volume of purified water by gavage once daily; 2. Poria cocos water extract group (FL): Poria cocos water extract was administered by gavage at a dose of 10g crude drug / kg body weight once daily; 3. Positive control group (ASLB): Oxaliplatin was administered intraperitoneally at a dose of 5 mg / kg body weight every 2 days.

[0049] The first administration was on the 4th day after surgery, and the medication was administered continuously for 12 days.

[0050] (iv) Live imaging monitoring Tumor growth was monitored using an in vivo bioluminescence imaging system during drug administration. 1. Before imaging, mice were injected intraperitoneally with 200 μL of LD-fluorescein potassium salt solution and left to stand in the dark for 3 min; 2. Subsequently, the mice were anesthetized by intraperitoneal injection of 300 μL of 5% tribromoethanol. After anesthesia (approximately 5-8 minutes after injection), the mice were placed in the imaging device. 3. Set imaging parameters: exposure time 10s, signal acquisition range 800-6000, acquire tumor bioluminescence signal, save image and analyze tumor burden.

[0051] (v) Specimen collection and testing After administration, the mice were euthanized by cervical dislocation, and the following tests were performed: 1. Dissect and separate the tumor tissue, and weigh it using an electronic balance; at the same time, dissect the abdominal cavity and count the number of metastatic nodules on the peritoneum and intestinal surface; 2. Peritoneal, intestinal, and liver tissues were collected, fixed with 4% paraformaldehyde, routinely embedded in paraffin, sectioned, stained with hematoxylin and eosin (HE), and the tumor infiltration was observed under an optical microscope. 3. Take tumor tissue and analyze differentially expressed proteins using quantitative proteomics technology.

[0052] (vi) Experimental Results 1. Impact on tumor growth: In vivo imaging and tumor weight results are shown in [reference needed]. Figure 2 In the model control group, the tumor bioluminescence signal of mice was strong, and the average tumor weight was 2.4±1.1g; in the Poria cocos group, the tumor signal was significantly weakened, and the average tumor weight decreased to 1.1±0.6g. The difference between the two groups was statistically significant (*p<0.05), suggesting that the water extract of Poria cocos can significantly inhibit the in vivo proliferation of gastric cancer tumors, and its tumor-inhibiting effect is comparable to that of the positive control drug oxaliplatin.

[0053] 2. Effects on peritoneal and organ metastasis: HE staining results are shown in [the table below]. Figure 3 In the control group, large areas of tumor cell infiltration and tissue morphology destruction were observed in the peritoneum, intestine, and liver tissues of mice. In the Poria cocos group, the tumor infiltration range was significantly reduced in all tissues, and the intestinal wall structure remained basically intact, suggesting that the water extract of Poria cocos can significantly inhibit the peritoneal and distant organ infiltration of gastric cancer cells.

[0054] 3. Impact on intestinal metastatic nodules: Gross specimens and quantitative statistical results are shown in [reference needed]. Figure 4 The intestinal surface of mice in the model control group was covered with a large number of metastatic nodules, with an average number of nodules of 13±5. The intestinal surface of mice in the Poria cocos group was smooth, and the number of nodules was significantly reduced to about 2. The difference was extremely significant compared with the model control group (**p<0.01), but there was no significant difference compared with the oxaliplatin group. This indicates that the water extract of Poria cocos can effectively inhibit the intestinal metastasis of gastric cancer.

[0055] 4. Effects on protein expression in tumor tissue: Proteomics analysis results are shown below. Figure 5 Compared with the model control group, the expression levels of multiple tumor suppressor genes, such as Fem1b, Ifi202, Dmbt1, Filip1l, Myh11, and Ltf, were significantly upregulated in the tumor tissues of mice treated with Poria cocos.

[0056] In summary, this embodiment demonstrates that oral administration of Poria cocos aqueous extract can significantly inhibit the proliferation of gastric cancer tumors and peritoneal and intestinal metastases, and its mechanism of action is related to the upregulation of tumor suppressor genes such as Fem1b.

[0057] Example 3: Effect of Fem1b knockdown on the invasive and metastatic ability of gastric cancer cells (a) Experimental materials • Cells: Human gastric cancer MKN-45 cells; • Reagents: Fem1b siRNA, transfection reagent, Poria cocos water extract (8%, v / v), crystal violet staining solution, RIPA lysis buffer, Fem1b primary antibody, actin internal control antibody, etc.

[0058] (II) Experimental Grouping and Treatment Set up 4 processing groups: 1. Blank control group: No treatment; 2. Poria cocos treatment group: Poria cocos water extract with a final concentration of 8% (v / v) was added; 3. Fem1b knockdown group: transfected with Fem1b siRNA; 4. Knockdown + Poria cocos combined treatment group: After transfection with Fem1bsiRNA, 8% (v / v) Poria cocos water extract was added.

[0059] (III) Detection Indicators and Methods 1. Western Blot Detection: After 48 h of treatment, cells from each group were collected, total protein was extracted, and after SDS-PAGE electrophoresis, transfer to a membrane, and blocking, Fem1b primary antibody (1:1000) and actin internal control antibody (1:5000) were added for incubation. After incubation with HRP-labeled secondary antibody, protein expression levels were detected by ECL chemiluminescence method to verify the siRNA knockdown efficiency and the effect of Poria cocos on Fem1b expression.

[0060] 2. Transwell migration assay: The treated cells were seeded in the upper chamber of a Transwell, and the lower chamber was filled with culture medium containing 10% fetal bovine serum. After culturing for 24 h, the cells were fixed with 4% paraformaldehyde, stained with crystal violet, and observed and counted under an optical microscope to assess the cell migration ability.

[0061] (iv) Experimental Results See results Figure 6 Western Blot results showed that Fem1b siRNA could effectively silence Fem1b expression in MKN-45 cells; treatment with Poria cocos water extract could significantly upregulate the basal expression of Fem1b in cells.

[0062] Transwell assay results showed that the number of transmembrane cells was significantly reduced in the Poria cocos treatment group, suggesting that Poria cocos can significantly inhibit the invasion and migration of gastric cancer cells; while the number of transmembrane cells was significantly increased in the Fem1b knockdown group, and the cell invasion and migration ability was enhanced; in the combined treatment group, Fem1b knockdown could significantly reverse the inhibitory effect of Poria cocos on cell invasion and migration.

[0063] The above results confirm that Fem1b is a tumor suppressor gene for gastric cancer and a key target for the anti-gastric cancer invasion and metastasis effect of Poria cocos water extract.

[0064] Example 4: In vivo safety evaluation of Poria cocos water extract (I) Experimental Methods Mice from the groups described in Example 2 were sacrificed after drug administration. The heart, liver, spleen, lungs, and both kidneys were quickly separated, and surface fat, fascia, and blood vessels were removed. Surface blood was blotted dry with filter paper, and the weight of each organ was measured using an electronic balance. Organ indices were calculated. Organ index (%) = Organ weight (g) / Mouse body weight (g) × 100% (II) Experimental Results The results of organ index statistics are shown below. Figure 7 Compared with the model control group, there were no significant differences in the heart, liver, lung, and kidney indices of mice in the 10g / kg Poria cocos administration group (ns, p>0.05); although the spleen index was slightly lower, the difference was not statistically significant compared with the model control group (p>0.05), only the spleen index of the positive control group (oxaliplatin) mice was significantly lower than that of the model control group (**p<0.01).

[0065] The results showed that, at the effective dose in this experiment, the aqueous extract of Poria cocos did not cause significant toxic damage to the major organs of mice, such as the heart, liver, spleen, lungs, and kidneys, and had good safety for in vivo application.

[0066] Explanation of Statistical Methods All experimental data were statistically analyzed using SPSS 22.0 software. Quantitative data were expressed as mean ± standard deviation (Mean ± SD). One-way ANOVA was used for comparisons among multiple groups, and LSD-t test was used for pairwise comparisons between groups. p < 0.05 was considered statistically significant, and p < 0.01 was considered extremely statistically significant.

Claims

1. The use of Poria cocos or its extracts in the preparation of drugs for the prevention of peritoneal metastasis of gastric cancer.

2. The application as described in claim 1, characterized in that, The drug is administered orally.

3. The application as described in claim 1 or 2, characterized in that, The poria cocos mentioned is the dried sclerotium of the fungus Poriacocos (Schw.) Wolf, belonging to the Polyporaceae family.

4. The application as described in claim 3, characterized in that, The dosage of the drug, calculated based on raw Poria cocos, is 8-12 g / kg body weight per day.

5. The application as described in claim 4, characterized in that, The dosage is 10g / kg body weight per day, calculated based on raw Poria cocos.

6. The application as described in any one of claims 1–5, characterized in that, The drug is used during the perioperative period of surgical resection of the primary gastric cancer lesion.

7. The application as described in claim 1, characterized in that, The Poria cocos or its extract prevents peritoneal metastasis of gastric cancer by upregulating the expression of tumor suppressor genes; the tumor suppressor genes are selected from one or more of Fem1b, Ifi202, Dmbt1, Filip1l, Myh11, Ltf, Faap100, Camp, Gmcl1, Uvssa, B9d1, Snca, Cntn3, Hspb6, Apoa2, Apoa1, Ahsg, Arhgap32, Ambp, Aldh1a1, Wdr47, Orm1, Mug1, and Gpld1.

8. A pharmaceutical composition for preventing peritoneal metastasis of gastric cancer, characterized in that, The pharmaceutical composition comprises a therapeutically effective amount of Poria cocos and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition according to claim 8, characterized in that, The pharmaceutical composition is an oral preparation.

10. The pharmaceutical composition according to claim 8, characterized in that, The Poria cocos exists in the pharmaceutical composition in the form of an aqueous extract or other extracts.

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