Application of schisandrin B in sensitizing 5-fluorouracil to treat colorectal cancer

Abstract

The invention provides an application of schisandrin b in sensitizing 5-fluorouracil to treat colorectal cancer. The schisandrin B inhibits a drug efflux transporter ATP (adenosine triphosphate) binding box subfamily C member 11 (ABCC11) by targeting a transcription factor DRAP1, increases the intracellular exposure concentration of 5-FU, and achieves the effect of sensitizing the 5-FU. The schisandrin B can effectively solve the problem that the remission rate of 5-FU for treating cancer is low, and can become a main component in the medicine for treating colorectal cancer.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and relates to the application of schisandrin B in the treatment of colorectal cancer with a sensitizing chemotherapy drug (5-fluorouracil), and also relates to a corresponding drug combination for treating colorectal cancer and a new application of schisandrin B in inhibiting the ubiquitination of the transcription factor DRAP1. Background Art

[0002] Colorectal cancer (CRC) is an important public health issue worldwide. There are approximately 20 million new cancer cases and 9.7 million cancer deaths each year worldwide. The incidence and mortality of CRC rank third and second among all cancer types, accounting for approximately 9.6% of new cases and 9.3% of deaths. In China, the number of new CRC cases reached 517,000, ranking second among all cancer types. The burden of CRC on health and medical care is increasing.

[0003] 5-Fluorouracil (5-FU) remains the most important drug for the treatment of CRC. 5-FU needs to be converted into active metabolites in cells, and it works by inhibiting the de novo biosynthesis of pyrimidine or interfering with the synthesis of macromolecules (such as DNA and RNA) as a pseudosubstrate and inhibiting normal function. Although 5-FU and its prodrugs capecitabine and tegafur have been widely used in clinical practice, the overall remission rate of the 5-FU combined with folinic acid (LV) regimen is still not ideal (22.3%), and the progression-free survival (PFS) is 6.2 months (median). In addition, the 3-year and 5-year overall survival (OS) rates of CRC patients receiving 5-FU chemotherapy were 72.2% and 60%, respectively, while the 5-year overall survival rate of metastatic CRC (mCRC) dropped sharply to 18.3%. In addition, nearly half of mCRC patients develop resistance to 5-FU-based chemotherapy, and this refractory CRC is usually caused by increased efflux of 5-FU or its active metabolites, mutations in the degrading enzymes of 5-FU or its prodrugs, etc. The increased efflux of 5-FU leading to low intracellular exposure levels is one of the important mechanisms for the development of its drug resistance, and the development of drug resistance is one of the main factors leading to treatment failure, which can lead to disease progression and even death.

[0004] Schisandrin B (Sch B) is a biphenylcyclooctene lignan extracted from the traditional Chinese medicine Schisandrin chinensis, which has multiple pharmacological effects such as liver protection, anti-inflammatory, anti-tumor and antioxidant. The anti-tumor effect of Schisandrin B is reflected in inhibiting tumor cell proliferation and inducing apoptosis, inhibiting tumor cell invasion and migration, inhibiting angiogenesis in tumors, reversing multidrug resistance of tumor cells, and enhancing the effect of chemotherapy drugs.

[0005] At present, the direct anti-tumor target of Schisandrin B is still unclear, and its mechanism of reversing multidrug resistance is also unclear. After arduous efforts, the inventors found that Schisandrin B can regulate the drug efflux transporter ABCC11 by targeting the transcriptional repressor DRAP1, increase the exposure level of 5-FU in tumor cells, and thus sensitize the anti-tumor effect of 5-FU. Summary of the invention

[0006] The present invention is aimed at the above problems, provides a new use of schisandrin B in treating colorectal cancer resistance and sensitization, further provides its use in sensitizing 5-fluorouracil to treat colorectal cancer, and explores the mechanism at the same time, and finds that it regulates ABCC11 by targeted inhibition of DRAP1 protein to sensitize colorectal cancer treatment and alleviate colorectal cancer resistance.

[0007] The research process of the present invention is as follows:

[0008] First, it was discovered that schisandrin B increased the anti-tumor effect of 5-FU on CRC tumor cells; then, the mechanism was explored and it was found that schisandrin B increased the intracellular exposure level of 5-FU by downregulating the ABCC11 transporter, further confirming that schisandrin B sensitizes 5-FU and improves 5-FU resistance by directly targeting the transcription factor DRAP1.

[0009] Based on the research content, the technical solutions to be protected by the present invention are as follows:

[0010] In the first aspect of the present invention, a use of Schisandrin B in the preparation of a 5-fluorouracil sensitizer is provided. The effect has been confirmed in cell and animal model experiments.

[0011] The results of in vitro cell experiments showed that the combined treatment of HCT116 cells with 5-FU (500 nM) and Sch B (1000 nM) could significantly reduce the formation of clonal colonies and induce cell apoptosis; the results of animal model experiments showed that compared with the Ctrl-5-FU group, the tumor volume and weight of the Ctrl-5-FU+Sch B group were significantly reduced, and when 5-FU was combined with Sch B, the exposure level of 5-FU was significantly increased.

[0012] Preferably, the sensitizer is a preparation that inhibits the level of ATP-binding cassette subfamily C member 11 (ABCC11) transporter; further preferably, the sensitizer is a preparation that directly targets and inhibits the transcription factor DRAP1 and inhibits its ubiquitination degradation.

[0013] In a second aspect of the present invention, a combination of schisandrin B and 5-fluorouracil is provided for the preparation of an anti-tumor drug, which can be applied to tumors that are treated with 5-fluorouracil for chemotherapy. 5-fluorouracil is mainly used for the treatment of digestive system tumors (such as colorectal cancer, gastric cancer, esophageal cancer, etc.) and breast cancer, so schisandrin B and 5-fluorouracil can be used in combination to treat these tumors.

[0014] In the present invention, it is found that schisandrin B can inhibit the drug efflux transporter ABCC11: LC-MS / MS is used to detect the concentration of 5-FU inside and outside HCT116 cells, and the intracellular 5-FU concentration of schisandrin B combined with 5-FU increases. Metabolomics is used to compare the metabolite differences between the schisandrin B group and the blank control group. The results show that there are significant differences in the metabolites of schisandrin B and the blank control group, which are mainly related to the leukotriene transport process. Leukotriene is an endogenous specific substrate of ABCC11. After schisandrin B treats cells, leukotriene accumulates in cells. qPCR is further used to determine that the level of ABCC11 is downregulated. In other words, schisandrin B mainly increases the exposure level of 5-FU by downregulating ABCC11.

[0015] It was further discovered that schisandrin B plays a role in sensitizing 5-FU and improving 5-FU resistance by directly targeting the transcription factor DRAP1: First, through mass spectrometry-cell thermal shift analysis experiments, it was found that schisandrin B may specifically bind to the DRAP1 protein. In order to further confirm the selectivity of schisandrin B for DRAP1, we used recombinant human DRAP1 protein and surface plasmon resonance experimental technology to detect the interaction between schisandrin B and protein, and found that schisandrin B can directly target the DRAP1 protein.

[0016] Subsequently, ubiquitination experiments were used to investigate the inhibitory effect of schisandrin B on the ubiquitination of DRAP1. It was found that schisandrin B inhibited the ubiquitination degradation of DRAP1 protein, and this effect was related to its targeting of the glutamate site 94 of DRAP1.

[0017] We further explored whether DRAP1 was related to the drug efflux transporter ABCC11 that we explored earlier. We found that after DRAP1 overexpression, the expression of ABCC11 was significantly reduced, while after DRAP1 knockout, the expression of ABCC11 was significantly increased. We then tested the cell viability after DRAP1 knockout and overexpression and then treated with 5-FU. After DRAP1 knockout, the anti-tumor effect of 5-FU was weakened, and after DRAP1 overexpression, the anti-tumor effect of 5-FU was enhanced. Therefore, we concluded that DRAP1 can indeed negatively regulate ABCC11 expression and affect the anti-tumor effect of 5-FU.

[0018] A subcutaneous xenograft model was established using human colorectal cancer HCT116 cells, and the expression of DRAP1 was silenced using adeno-associated virus (AAV). Mice were given PBS or schisandrin B (30 mg / kg), or 5-FU (25 mg / kg), or 5-FU (25 mg / kg) + schisandrin B (30 mg / kg). After 21 days of drug treatment, all mice were killed. We found that the tumor volume growth rate of mice in the combination group slowed down, and after silencing DRAP1, the therapeutic effect of schisandrin B was significantly reduced, suggesting that schisandrin B mainly exerts its tumor treatment effect by binding to DRAP1.

[0019] The present invention first discovered that schisandrin B inhibits DRAP1 ubiquitination degradation in tumors. Therefore, the third aspect of the present invention provides the use of schisandrin B in the preparation of DRAP1 ubiquitination degradation inhibitors. Preferably, the site of DRAP1 directly targeted by schisandrin B is glutamic acid at position 94, and inhibits DRAP1 ubiquitination degradation.

[0020] In a fourth aspect, the present invention provides the use of schisandrin B in the preparation of a drug for treating colorectal cancer. Preferably, the active ingredient of the drug for treating colorectal cancer is schisandrin B or a combination of schisandrin B and 5-fluorouracil.

[0021] According to the above description, Schisandrin B inhibits DRAP1 ubiquitination degradation in tumors, and tumors with mechanisms related to DRAP1 ubiquitination degradation can be treated with Schisandrin B. The therapeutic effects include increasing apoptosis of colorectal cancer cells, inhibiting proliferation, increasing the ability of invasion and migration, and inhibiting the growth of tumors in the body.

[0022] The combination of schisandrin B and 5-fluorouracil is used to treat tumors treated with 5-fluorouracil chemotherapy and to sensitize the resistance to 5-FU.

[0023] In a fifth aspect, the present invention provides a drug for treating colorectal cancer, comprising a combined drug composition 1 and a drug composition 2, wherein the drug composition 1 is composed of schisandrin B and pharmaceutically acceptable excipients, and the drug composition 2 is composed of 5-fluorouracil and pharmaceutically acceptable excipients.

[0024] In addition, the colorectal cancer therapeutic drug can also be composed of schisandrin B and pharmaceutically acceptable adjuvants. The pharmaceutical composition of the present invention can be various preparations prepared by combining schisandrin B and pharmaceutically acceptable adjuvants, preferably solid preparations and liquid preparations. The preparation of the present invention can be in unit dosage form, such as tablets, pills, capsules (including sustained release or delayed release forms), powders, suspensions, granules, tinctures, syrups, emulsions, suspensions, injections, etc. and various sustained-release dosage forms, so as to be suitable for various modes of administration.

[0025] The innovativeness of the technical solution of the present invention is as follows:

[0026] The present invention found that schisandrin B increased the anti-tumor effect of 5-FU on CRC tumor cells, and verified it through cell and animal model experiments. Schisandrin B can effectively solve the problem of low remission rate of 5-FU in the treatment of colorectal cancer, and can become the main component of colorectal cancer treatment drugs. Then the mechanism was explored, and it was found that schisandrin B increased the intracellular exposure level of 5-FU by down-regulating the ABCC11 transporter. It was further confirmed that schisandrin B directly targeted the transcription factor DRAP1, down-regulated the ABCC11 transporter, played a role in sensitizing 5-FU and improving 5-FU resistance. It was found for the first time that schisandrin B inhibited the ubiquitination degradation of DRAP1 in tumors, and can be used to treat tumors related to the mechanism and ubiquitination degradation of DRAP1. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 It was shown that schisandrin B increased the antitumor effect of 5-FU on CRC tumor cells;

[0028] Figure 2 It was shown that schisandrin B increased the intracellular exposure level of 5-FU by downregulating the ABCC11 transporter;

[0029] Figure 3 It was shown that schisandrin B directly binds to DRAP1 and inhibits its ubiquitination and degradation;

[0030] Figure 4 It was shown that inhibition of ABCC11 by schisandrin increased the sensitivity to 5-FU;

[0031] Figure 5 It was shown that schisandrin B inhibited the expression of ABCC11 by targeting DRAP1;

[0032] Figure 6 The effects of schisandrin B on subcutaneous colorectal cancer xenograft tumors in mice are shown. DETAILED DESCRIPTION

[0033] The following examples and experimental examples are provided to further illustrate the present invention and should not be construed as limiting the present invention. The examples do not include a detailed description of conventional methods, which are well known to those skilled in the art and are described in many publications.

[0034] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention, and the preferred implementation methods and materials described in the specific embodiments are for demonstration purposes only.

[0035] Example 1 Application of Schisandrin B in Sensitizing 5-Fluorouracil (5-FU) in the Treatment of Colorectal Cancer

[0036] HCT116 cells were seeded into 96-well plates overnight, and then treated with different concentrations of Sch B or 5-FU for 24 or 48 hours. Cell proliferation was determined using the Cell Counting Kit-8 (CCK-8). The absorbance of the reaction was measured at a wavelength of 450 nm. To evaluate the synergistic effect of 5-FU and Sch B, 5-FU and Sch B were added alone or in combination (0+0, 25+0, 0+75, 25+75 μM, different groups) for 48 hours. The combination index was calculated as R=[survival(A+B) / survival(A)*survival(B)].

[0037] The data showed that the combination index (CI) of the two drugs was R=0.608, showing a significant synergistic effect ( Figure 1 A). Primary CRC cells were extracted from tumors resected from 19 CRC patients and treated with 5-FU (25 μM) alone or Sch B (75 μM) alone or in combination. The results showed that Schisandrin B enhanced the inhibitory effect of 5-FU on primary CRC cells from all 19 patients (1B). In addition, HCT116 cells were cultured in a 6-well plate at a concentration of 2 × 10^6 cells / well. A straight scratch was formed by directly scratching the cell monolayer with a pipette tip in the culture dish. The cells were treated with different concentrations of 5-FU (0, 25 μM) and Sch B (0, 75 μM). HCT116 cells were treated with 5-FU (500 nM) and Sch B (1000 nM) in combination, and photographed and recorded every 24 hours until 96 hours. It was found that 5-FU combined with Sch B inhibited the scratch healing of HCT116 cells ( Figure 1C). A clone formation experiment was also performed. When visible clones appeared in the culture dish, the culture was terminated, the culture medium was discarded, and the cells were carefully washed twice with PBS solution and air-dried. The cells were fixed with methanol for 15 minutes, and the methanol was discarded and air-dried. The cells were stained with Giemsa stain for 10 minutes, and the stain was slowly washed away with running water. The plate was inverted and a transparent film with a grid was superimposed, and the clones were counted directly with the naked eye. We found that the combined treatment of HCT116 cells with 5-FU (500 nM) and Sch B (1000 nM) significantly reduced the formation of clonal colonies ( Figure 1 D) Tunel staining revealed that the combined treatment of the two drugs can induce cell apoptosis ( Figure 1 E).

[0038] Example 2 Schisandrin B can downregulate ABCC11 transporter and increase the intracellular exposure level of 5-FU

[0039] To explore the intrinsic mechanism by which Sch B enhances the anti-tumor effect of 5-FU, we cultured HCT116 cells at a concentration of 2 × 10^6 cells / well in 6-well plates. The next day, the cells were treated with vehicle or Sch B (75 μM) and 5-FU (25 μM) or their combination for 24 h. The cells were lysed with cold methanol to extract metabolites, and the volume of cold methanol was normalized according to the number of cells. The exposure level of 5-FU in HCT116 cells when combined with Sch B was detected. The results showed that after combination with Sch B, the exposure level of 5-FU in single cells was significantly increased ( Figure 2 A). We further performed non-targeted metabolomics to compare whether Schisandrin B improved the metabolism of HCT116 cells. Non-targeted metabolomics was consistent with the above treatment methods, and the data were processed using Progenesis® QI (version 2.0), EZinfor 3.0, or SIMCA 14.1 software23. The OPLS-DA model showed that the blank group was significantly different from the Sch B group ( Figure 2 B: Posi, R2X=1, Q2=1), in which, this study found that the endogenous substrate of the ABCC11 transporter, leukotriene metabolites, accumulated in cells and accumulated when Sch B was added to treat the cells ( Figure 2 C). This study further measured the expression level of ABCC11 and found that Sch B significantly inhibited the expression of ABCC11 ( Figure 2 D). ABCC11 plays a key role in Sch B enhancing the anticancer effect of 5-FU.

[0040] Example 3 Schisandrin B directly binds to DRAP1 and inhibits its ubiquitination degradation

[0041] The targets of schisandrin B were analyzed by cell thermal shift-mass spectrometry experiments. The cells treated or untreated with schisandrin B were divided into ten equal parts. The 10 samples were heated at different temperatures (37-67°C) for 3 minutes and then subjected to 4D-DIA MS analysis. The results showed that more than 9,150 proteins and 110,079 peptide chains were detected and identified. Most importantly, DRAP1 (a transcriptional repressor, also known as NC2alpha) became more stable after treatment with schisandrin B, and its melting point increased from 54.17°C to 57.79°C ( Figure 3 A).

[0042] To further identify the target of Sch B, SPR assays were performed in this study. Different concentrations of Sch B (4 × 10-6, 8 × 10-6, 16 × 10-6, 32 × 10-6, 64 × 10-6, 108 × 10 - 6 and 0 × 10 - 6 M) were prepared with running buffer [PBST (0.1% Tween 20), pH 5 and 8% DMSO]. Super streptavidin biosensor (Forte ′ Bio Inc. 4 Biotin (Pierce) was captured on the sensor CM5 surface. After reaching the baseline, the sensor was moved to the binding step for 60 seconds and then separated for 60 seconds. The curve was calibrated by the double reference technique using super streptavidin needles immersed in the experimental wells and reference wells (containing buffer only). The results showed that Sch B can bind specifically and strongly to DRAP1 with a KD value of 8.4*10^-5 ( Figure 3 B).

[0043] Following the same treatment method, we extracted proteins after administration of Schisandrae Chinensis B for Western Blot analysis, and we found that Schisandrae Chinensis B increased the stability of DRAP1 (3C). At the same time, we performed co-immunoprecipitation experiments and DRAP1 ubiquitination assays. The results showed that Schisandrae Chinensis B significantly inhibited the ubiquitination of DRAP1 after binding to DRAP1, and this effect was abolished when DRAP1 mutated to DRAP1-G94A ( Figure 3 D). In summary, schisandrin B can directly bind to the GLN-94 residue of DRAP1 and inhibit its ubiquitination.

[0044] Example 4 Schisandrin B inhibits ABCC11 and increases the sensitivity of 5-FU

[0045] To investigate whether the transcriptional repressor DRAP1 regulates ABCC11, we transfected siRNA or overexpressed DRAP1 with a DRAP1 vector plasmid, inoculated HCT116 cells at 2 × 10^6 cells / well and cultured them in a 6-well plate. On the second day, fluorescent siRNA or overexpression plasmid (OE) and transfection reagent were added. The transfection efficiency was observed by fluorescence 24 hours after transfection. When the confluence rate reached 90%, RNA was extracted for RT-qPCR experiments to observe the changes in ABCC11. The data showed that after DRAP1 was knocked out, the expression of ABCC11 was upregulated ( Figure 4 A); On the other hand, overexpression of DRAP1 can significantly inhibit the expression level of ABCC11 ( Figure 4 C).

[0046] Then, HCT116 cells were treated with 5-FU for 24 or 48 h after DRAP1 knockout or overexpression. The results showed that DRAP1 knockout reduced the sensitivity of HCT116 cells to 5-FU, and the cell survival rate was significantly higher than that of the 5-FU group ( Figure 4 B); On the contrary, upregulation of DRAP1 enhanced the anticancer effect of 5-FU on HCT116 cells, and the cell survival rate was significantly reduced compared with the 5-FU group ( Figure 4 D). Next, HCT116 cells were directly treated with Sch B, and the results showed that the expression level of DRAP1 increased, while the expression level of ABCC11 decreased (Figure 5A). However, after knocking out DRAP1, Sch B could not downregulate the expression of ABCC11 (Figure 5B). In conclusion, Sch B can reduce the expression level of ABCC11 by directly binding to DRAP1 and then inhibiting its ubiquitination degradation, ultimately sensitizing CRC cells to 5-FU treatment.

[0047] Example 5 Effect of Schisandrin B on Subcutaneous Colorectal Cancer Xenograft Tumors in Mice

[0048] The animal experiment protocol was approved by the Experimental Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval number: PZSHUTCM2402240001). Male BALB / c nude mice were purchased from Shanghai Bikekey Biotechnology Co., Ltd. All mice were housed in the animal center under a 12 / 12 h light-dark cycle at room temperature and fed with standard rodent chow and water. Animals were acclimated to the laboratory for at least 1 week before treatment. A small portion (5 × 106) of HCT 116 cells was suspended in 100 μL 1× PBS and then injected subcutaneously into the left abdomen of each mouse. After 13 days of inoculation (tumor volume: 100-200 m3), all mice were randomly assigned to the control adeno-associated virus group (Ctrl group, n = 20) or the DRAP1 interference adeno-associated virus group (AAV-DRAP1 group, n = 20) and injected with 25 μL (2*10^12 vg / mL) at the tumor site three times a week for one week to knock out DRAP1. Subsequently, the Ctrl group and AAV-DRAP1 group were randomly divided into four subgroups (n=5), and each subgroup was intraperitoneally injected with 1 mL / Kg PBS, or Sch B (30 mg / kg), or 5-FU (25 mg / kg), or 5-FU (25 mg / kg) + Sch B (30 mg / kg). After 21 days of drug treatment, all mice were killed and tumor samples were collected for analysis.

[0049] The experimental data showed that compared with the Ctrl-5-FU group, the tumor volume and weight of the Ctrl-5-FU+Sch B group were significantly reduced, but when DARP1 was knocked out, the synergistic effect of Sch B and 5-FU was significantly reduced, and the tumor volume and weight of the AAV-DRAP1-5-FU+Sch B group were similar to those of the AAV-DRAP1-5-FU group ( Figure 6 A, 6B). When 5-FU was combined with Sch B in the tumor, the exposure level of 5-FU increased significantly, but in DRAP1 knockout tumors, the level of 5-FU was significantly lower than that in the Ctrl-5-FU group, and the combined use of Sch B could not increase the level of 5-FU ( Figure 6 C). In addition, compared with the control group, the expression level of DRAP1 in the AAV-DARP1 group was significantly decreased, while the expression level of ABCC11 in the AAV-DRAP1 group was increased ( Figure 6 D). In summary, Sch B can directly bind to DRAP1 and downregulate the expression of ABCC11, thereby increasing the exposure level of 5-FU and enhancing its anti-tumor effect.

[0050] The unexplained parts involved in the present invention are the same as the prior art or are implemented by the prior art. The applicant declares that the present invention illustrates the detailed method of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned detailed method, that is, it does not mean that the present invention must rely on the above-mentioned detailed method to be implemented. Those skilled in the art should understand that any improvement of the present invention, the equivalent replacement of the raw materials of the product of the present invention, the addition of auxiliary components, the selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. Application of schisandrin B in the preparation of 5-fluorouracil sensitizer.

2. The use according to claim 1, characterized in that: The sensitizer is an agent that inhibits the level of ATP-binding cassette subfamily C member 11 (ABCC11) transporter.

3. The use according to claim 2, characterized in that: The sensitizer is a preparation that directly targets and inhibits the transcription factor DRAP1 and inhibits its ubiquitination degradation.

4. The application of schisandrin B and 5-fluorouracil in the preparation of anti-tumor drugs, characterized in that: The tumors include colorectal cancer, gastric cancer, esophageal cancer, breast cancer, and ovarian cancer.

5. Application of schisandrin B in the preparation of DRAP1 ubiquitination degradation inhibitors.

6. The use according to claim 5, characterized in that: Schisandrin B directly targets DRAP1 at glutamate 94 and inhibits DRAP1 ubiquitination and degradation.

7. Application of schisandrin B in the preparation of drugs for the treatment of colorectal cancer.

8. The use according to claim 7, characterized in that: The active component of the colorectal cancer treatment drug is schisandrin B or a combination of schisandrin B and 5-fluorouracil.

9. A drug for treating colorectal cancer, characterized in that: It comprises a combined pharmaceutical composition 1 and a pharmaceutical composition 2, wherein the pharmaceutical composition 1 is composed of schisandrin B and pharmaceutically acceptable excipients, and the pharmaceutical composition 2 is composed of 5-fluorouracil and pharmaceutically acceptable excipients.

10. A drug for treating colorectal cancer, characterized in that: The invention consists of schisandra chinensis B and pharmaceutically acceptable auxiliary materials.

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