Application of apiose platycodin D3 in preparation of medicine for treating digestive tract tumors

Abstract

The invention belongs to the technical field of medicines, and in particular relates to an application of apiose-platycodin D3 (Deapiose-platycodin D3, the molecular formula of which is C58H94O29, the molecular weight of which is 1255.36 and the CAS number of which is 67884-05-3) in preparation of a medicine for treating gastrointestinal tumors. Through cell proliferation experiments and clone formation experiments, it is verified for the first time that apiose platycodin D3 can effectively inhibit growth of human esophageal cancer, colorectal cancer and gastric cancer cells. The invention provides a new candidate drug and basis for clinical treatment and prevention of gastrointestinal tumors.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of the compound despico-salicylic acid saponin D3 in the preparation of drugs for treating gastrointestinal tumors. Background Technology

[0002] According to data from the 2022 Global Cancer Watch report, esophageal cancer ranks 11th in global cancer incidence and is the seventh leading cause of cancer-related deaths. Data shows that while the overall incidence of esophageal cancer is declining, it remains high in some high-incidence areas. Squamous cell carcinoma is dominant in East Asia, while adenocarcinoma is more common in Western countries. This regional difference reflects the combined effects of genetic background, environmental exposure, and lifestyle. In terms of diagnosis, early-stage esophageal cancer often presents with no obvious specific symptoms, and most patients are diagnosed at an advanced stage, limiting the application of radical surgery and directly leading to a poor overall prognosis. Traditional treatment mainly relies on surgery combined with radiotherapy and chemotherapy, but these methods alone are insufficient to significantly prolong the survival time of advanced-stage patients, and the 5-year survival rate remains low. With the in-depth development of molecular biology and tumor immunology, and the rapid advancement of precision medicine and immunotherapy research, molecularly targeted drugs and immune checkpoint inhibitors have gradually entered clinical trials and first- and second-line treatment strategies for esophageal cancer in recent years, showing superior efficacy compared to chemotherapy alone in some patients. For example, perioperative immunotherapy and drug combinations targeting VEGF / EGFR / HER2 are being evaluated for their potential in prolonging disease-free survival and overall survival. Nevertheless, existing immunotherapies and targeted therapies still face challenges such as limited efficacy, a narrow range of beneficiaries, and immune-related adverse reactions. For instance, immune checkpoint inhibitors may cause severe immune side effects in some patients, and more refined biomarkers are needed to predict which patients will truly benefit from these treatments. Therefore, the search for novel therapeutics with entirely new mechanisms of action that can effectively improve patient survival outcomes is particularly important and urgent.

[0003] Deadipin-platycodin D3 is a triterpenoid saponin derived from the roots of *Platycodon grandiflorum*, with the molecular formula C58H94O29. Existing research indicates that deadipin-platycodin D3 possesses biological activity in non-tumor disease models, maintaining cellular metabolic homeostasis and tissue structural integrity through direct binding to PTP1B and regulation of signaling pathways such as PKM2 / AMPK, thereby exerting a protective effect against diseases such as osteoarthritis. However, systematic reports on the direct antitumor activity and molecular mechanisms of deadipin-platycodin D3 in tumors are currently lacking. Given that homologous or structurally similar platycodon saponins have been shown to possess multi-target antitumor potential, deadipin-platycodin D3 may also have the potential for antitumor activity; its specific mechanisms and therapeutic value require further in-depth investigation. Summary of the Invention

[0004] The purpose of this invention is to overcome the defects of the prior art and provide a new application of the compound deapigenin-platycoside D3 in inhibiting the growth of gastrointestinal tumors. That is, this application has discovered a new use of the known compound deapigenin-platycoside D3.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] Deapi-platycodin D3, with the molecular formula C 58 H 94 O 29 The molecular weight is 1255.36, CAS number: 67884-05-3, and the structural formula is shown below:

[0007]

[0008] In the above applications, apigenin D3 significantly inhibited the proliferation and colony formation of gastrointestinal tumor cells in vitro.

[0009] This invention investigated the anti-gastrointestinal tumor activity of apigenin-free platycodon saponin D3, specifically its application in the preparation of drugs that inhibit the proliferation of gastrointestinal tumor cells. Specifically, this invention discovered that apigenin-free platycodon saponin D3 at concentrations of 20-200 μM can inhibit the proliferation and colony formation of esophageal cancer, colorectal cancer, and gastric cancer cells in vitro.

[0010] Compared with existing technologies, this invention has the following beneficial effects: Deapigenin D3 can effectively inhibit the proliferation and colony formation of esophageal cancer, gastric cancer, and colorectal cancer cells in vitro. This invention reports for the first time the antitumor activity of the compound deapigenin D3 in gastrointestinal tumors, providing a new approach for the clinical development of drugs for gastrointestinal tumors. Attached Figure Description

[0011] Figure 1 This study investigated the inhibitory effect of apigenin-free platycodon saponin D3 on gastrointestinal tumor cells. Specifically, A represents the inhibition of esophageal cancer cells (KYSE150, KYSE450, KYSE510), gastric cancer cells (HGC27), and colorectal cancer cells (SW480) by apigenin-free platycodon saponin D3 at concentrations ranging from 20 to 200 μM. B represents the inhibition of colony formation of the aforementioned gastrointestinal tumor cells by apigenin-free platycodon saponin D3 at concentrations ranging from 20 to 80 μM. (Compared to the control group, ns: p > 0.05, *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.0001) Figure 1 (See attached figure for the abstract of this invention) Detailed Implementation

[0012] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. The following embodiments are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention.

[0013] Materials and Methods

[0014] 1. Tumor cell lines

[0015] The esophageal cancer cells, gastric cancer cells, and colorectal cancer cells used in this invention were obtained from the Sino-US (Henan) Hormel Cancer Research Institute.

[0016] 2. Reagents

[0017] Penicillin: North China Pharmaceutical Co., Ltd.;

[0018] Streptomycin: Shandong Lukang Pharmaceutical Co., Ltd.;

[0019] 0.25% Pancreatic Enzyme: Shanghai Beyotime Biotechnology Co., Ltd.;

[0020] RPMI-1640 culture medium: Biological Industries, Israel;

[0021] PBS powder: Beijing Solarbio Science & Technology Co., Ltd.

[0022] MTT powder: Beijing Solarbio Technology Co., Ltd.;

[0023] Crystal violet powder: Tianjin Kemeo Chemical Reagent Co., Ltd.;

[0024] Fetal bovine serum: BI, Inc., USA;

[0025] DMSO: Tianjin Kemeo Chemical Reagent Co., Ltd.

[0026] Deapi-platycodin D3: Chengdu Manster Biotechnology Co., Ltd.;

[0027] 3. Instruments and Consumables

[0028] 1.5 mL centrifuge tubes: Axygen Corporation, USA;

[0029] 50 mL centrifuge tubes: Corning Corporation, USA;

[0030] 96-well cell culture plate: Wuxi NiceBiotechnology Co., Ltd.;

[0031] 6-well cell culture plate: Wuxi NiceBiotechnology Co., Ltd.;

[0032] 10 cm cell culture plate: Wuxi NiceBiotechnology Co., Ltd.;

[0033] Pipettes: Eppendorf GmbH, Germany;

[0034] Dry CO2 incubator: Shanghai Yiheng Scientific Instruments Co., Ltd.;

[0035] Milli-Q water purifier: Millipore, USA.

[0036] Experimental methods

[0037] Example 1: Cell proliferation experiment

[0038] On day 1, cells were seeded into plates with approximately 2000 cells per well. On day 2, culture medium containing apigenin D3 was added at concentrations of 0 μM, 20 μM, 40 μM, 60 μM, 80 μM, 100 μM, and 200 μM. After 72 h of drug treatment, 20 μL of LTT was added, and the plates were incubated at 37 ℃ in the dark for 2 h. The supernatant was discarded, and 150 μL of DMSO was added. The absorbance values ​​at 490 nm and 570 nm were measured using a microplate reader, and the statistical results were analyzed.

[0039] Example 2: Plate Colony Formation Experiment

[0040] On day 1, cells were seeded into plates, approximately 700 cells per well. On day 2, medium containing apigenin D3 was added at concentrations of 0 μM, 20 μM, 40 μM, 60 μM, and 80 μM. Cells were incubated until visible cell clones appeared, approximately 10 days later. Cells were stained with 0.5% crystal violet solution, and after staining, the 6-well plates were washed, air-dried, photographed, and the number of cell clones was counted.

[0041] Experimental results

[0042] Figure 1 This study demonstrates the inhibitory effect of apigenin D3 on the growth of esophageal cancer (KYSE150, KYSE450, KYSE510), gastric cancer (HGC27), and colorectal cancer (SW480) cells. Figure A shows a bar graph of tumor cell proliferation after 72 h of treatment with different concentrations of apigenin D3, indicating that apigenin D3 significantly inhibited the proliferation of all the aforementioned cancer cells within the concentration range of 20-200 μM, and the inhibitory effect was clearly concentration-dependent. Figure B shows images of tumor cell colony formation after apigenin D3 treatment and a statistical bar graph of the number of colonies formed, indicating that apigenin D3 significantly inhibited the colony-forming ability of the aforementioned cancer cells, and the number of colonies decreased with increasing drug concentration. (Statistical annotations in the figures: *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.0001 compared with the control group)

[0043] In summary, this invention demonstrates the anti-proliferative effect of the compound deapi-platycodin D3 on gastrointestinal tumor cells through in vitro cell experiments. Experimental results show that deapi-platycodin D3 significantly inhibits the proliferation and colony formation of esophageal cancer cells (KYSE150, KYSE450, KYSE510), gastric cancer cells (HGC27), and colorectal cancer cells (SW480). This invention is the first to clearly reveal the antitumor activity of deapi-platycodin D3 in gastrointestinal tumors, providing a novel approach for the clinical development of new therapeutic drugs for esophageal, gastric, and colorectal cancers.

[0044] This specific embodiment is only for explaining and illustrating the technical solution of the present invention, and its content should not be construed as limiting the scope of protection of the present invention. Those skilled in the art can make modifications to this embodiment without contributing any inventive step after reading this specification, but such modifications are protected by patent law as long as they fall within the scope of the claims of the present invention.

Claims

1. Use of deapiopseudookanin D3 in the preparation of a drug for treating a digestive tract tumor.

2. Use according to claim 1, characterized in that, The digestive tract tumor is esophageal cancer, colorectal cancer, and gastric cancer.

3. Use according to claim 1, characterized in that, The esophageal cancer is esophageal squamous cell carcinoma.

4. Use according to claim 1, characterized in that, The deapiopseudookanin D3 exerts an anti-tumor effect by inhibiting the proliferation and clonogenic ability of digestive tract tumor cells.

5. The use according to claim 1, characterized in that, The deapiopseudookanin D3 is formulated with a pharmaceutically acceptable carrier or excipient for an anti-tumor pharmaceutical composition.

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