Use of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine for preparing colorectal cancer chemotherapeutic drug sensitizer

Abstract

The present invention provides use of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine for preparing a colorectal cancer chemotherapeutic drug sensitizer. The glycerophospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine provided by the present invention can be used for preparing a drug that increases the sensitivity of patients with intestinal cancer to oxaliplatin and / or capecitabine drugs, especially by regulating the cell membrane function and enhancing the drug sensitivity, thereby improving the therapeutic effect of chemotherapy for intestinal cancer.

Description

Use of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline in the preparation of sensitizers for colorectal cancer chemotherapy drugs. Technical Field

[0001] This invention relates to the field of lipid metabolism function and application technology, and in particular to the use of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline in the preparation of a sensitizer for colorectal cancer chemotherapy drugs. Background Technology

[0002] Colorectal cancer is one of the most common malignant tumors in my country. While survival rates have improved with advancements in early diagnosis and surgical treatment, the treatment of advanced colorectal cancer still faces significant challenges. Chemotherapy, as a core component of comprehensive colorectal cancer treatment, is widely used in the treatment of advanced-stage patients, especially as adjuvant therapy after surgery and in the treatment of metastatic disease.

[0003] Oxaliplatin and capecitabine are commonly used chemotherapy drugs for colorectal cancer, and they have been shown to play an important role in improving patient prognosis. Oxaliplatin, as a third-generation platinum-based compound, inhibits tumor growth by binding to DNA and suppressing the division and proliferation of tumor cells. Capecitabine, on the other hand, is a fluorouracil-based drug that exerts its anti-tumor effect by interfering with the DNA synthesis of tumor cells.

[0004] However, colorectal cancer patients often face chemotherapy resistance during chemotherapy, which significantly reduces treatment effectiveness and consequently affects patient survival. Chemotherapy resistance can be divided into primary and secondary resistance. Primary resistance refers to the tumor's resistance to the drug before chemotherapy begins, while secondary resistance occurs during chemotherapy when tumor cells adapt to the pressure of the chemotherapeutic drugs, thus acquiring new resistance. Resistance to oxaliplatin and capecitabine, in particular, has become a major challenge in the treatment of colorectal cancer. The mechanisms of oxaliplatin resistance are complex, involving multiple resistance pathways in tumor cells, such as overexpression of drug efflux pumps, alterations in DNA repair mechanisms, and adaptive changes in the tumor microenvironment. Similarly, capecitabine resistance mechanisms include reduced drug uptake by tumor cells and alterations in their metabolic pathways.

[0005] Overcoming chemotherapy resistance in colorectal cancer, particularly resistance to oxaliplatin and capecitabine, is a pressing challenge in the field of oncology treatment. The CAPOX regimen, a neoadjuvant chemotherapy regimen for colorectal cancer, is a commonly used treatment for advanced rectal cancer. The CAPOX regimen consists of two drugs: oxaliplatin and capecitabine. CAPOX plays a crucial role in neoadjuvant chemotherapy for colorectal cancer and is one of the most widely used treatment options in clinical practice.

[0006] Therefore, studying the molecular mechanisms of reversing oxaliplatin and capecitabine resistance in colorectal cancer, and finding new targets and treatment strategies, is of great clinical significance for improving the efficacy of chemotherapy and improving patient prognosis. Summary of the Invention

[0007] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide a use of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine in the preparation of a sensitizer for colorectal cancer chemotherapy drugs, in order to solve the problem of chemotherapy resistance that colorectal cancer patients often face during chemotherapy.

[0008] To achieve the above and other related objectives, the present invention provides the use of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline in the preparation of a sensitizer for colorectal cancer chemotherapy drugs.

[0009] Preferably, the chemotherapy drug for colorectal cancer is oxaliplatin and / or capecitabine.

[0010] The present invention also provides a sensitizer for colorectal cancer chemotherapy drugs, comprising at least 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine.

[0011] Preferably, the colorectal cancer chemotherapy drug sensitizer is an oxaliplatin sensitizer and / or a capecitabine sensitizer.

[0012] The present invention also provides the use of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline in the preparation of a medicament that increases the sensitivity of colorectal cancer patients to oxaliplatin and / or capecitabine.

[0013] The present invention also provides the use of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline for improving the sensitivity of colorectal cancer cells to oxaliplatin and / or capecitabine.

[0014] Preferably, the sensitivity of colon cancer cells to oxaliplatin and / or capecitabine is enhanced by regulating the function of the colon cancer cell membrane with 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline.

[0015] As described above, the present invention has the following beneficial effects: the glycerophospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate choline (1-Palmitoyl-2-oleoyl-sn-glycero-3-PC) provided by the present invention can be used to prepare drugs that increase the sensitivity of colorectal cancer patients to oxaliplatin and / or capecitabine, especially by regulating cell membrane function and enhancing drug sensitivity, thereby improving the efficacy of colorectal cancer chemotherapy. Attached Figure Description

[0016] Figure 1 shows the results of metabolomics analysis of glycerophospholipid PC (18:0 / 0:0) (A) and 1-Palmitoyl-2-oleoyl-sn-glycero-3-PC (POPC) (B) in tumors and adjacent normal tissues of colorectal cancer patients resistant to neoadjuvant chemotherapy CAPOX.

[0017] Figure 2 shows the experimental results of POPC increasing the cell viability and proliferation inhibition of colorectal cancer cells induced by oxaliplatin and capecitabine. (A) shows the cell viability of HCT116 cells after treatment with capecitabine and POPC or PC (18:0 / 0:0) using CCK8 assay; (B) shows the cell viability of HCT116 cells after treatment with oxaliplatin and POPC or PC (18:0 / 0:0) using CCK8 assay; and (C) shows the results of IC50 assay using capecitabine and POPC on HCT116 cell lines. 50 Quantitative analysis; (D) shows the results of IC50 assay using HCT116 cell line treated with a combination of oxaliplatin and POPC. 50 Quantitative analysis; (E) shows the results of IC50 assay using HCT116 cell line treated with a combination of oxaliplatin and POPC. 50 Quantitative analysis; (F) shows the results of IC50 assay using HCT116 cell line treated with capecitabine and PC (18:0 / 0:0). 50 Quantitative analysis; ns: no statistically significant difference; **P<0.001: significant difference.

[0018] Figure 3 shows the experimental results of silencing ATXN2L cells to reverse oxaliplatin-induced resistance in gastric cancer cells. (A) shows the apoptosis experiment performed on HCT116 cell lines treated with a combination of oxaliplatin and POPC. Cells were stained with Annexin V / PI apoptosis detection reagent, and apoptosis was detected by ultra-high-speed flow cytometry. (B) shows the statistical graph of apoptosis detection results obtained from three independent experiments. **P<0.001: statistically significant difference. (C) shows the apoptosis experiment performed on HCT116 cell lines treated with a combination of capecitabine and POPC. Cells were stained with Annexin V / PI apoptosis detection reagent, and apoptosis was detected by ultra-high-speed flow cytometry. After staining with V / PI apoptosis detection reagent, cell apoptosis was detected by ultra-high-speed flow cytometry; (D) shows a statistical graph of apoptosis detection results obtained from three independent experiments, **P<0.001: significant difference; (E) shows the sensitizing effect of POPC on oxaliplatin using a colony formation assay; (F) shows a statistical graph of colony formation assay results obtained from three independent experiments, **P<0.001: significant difference; (G) shows the sensitizing effect of POPC on capecitabine using a colony formation assay; (H) shows a statistical graph of colony formation assay results obtained from three independent experiments, **P<0.001: significant difference. Detailed Implementation

[0019] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention; in the specification and claims of the present invention, unless otherwise expressly stated in the text, the singular forms "a", "an" and "this" include the plural forms.

[0020] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, apparatus, and materials similar to or equivalent to those described, apparatus, and materials in the embodiments of this invention may be used to implement the present invention.

[0021] Unless otherwise stated, the experimental methods, detection methods, and preparation methods disclosed in this invention all employ conventional techniques in molecular biology, biochemistry, chromatin structure and analysis, analytical chemistry, cell culture, recombinant DNA technology, and related fields.

[0022] The following compounds and intermediates were characterized by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). The starting materials and reagents used in the preparation of these compounds were available from suppliers or prepared by methods known to those skilled in the art. The following general synthetic routes are merely illustrative of methods by which the compounds of the present invention can be synthesized, and various modifications to these synthetic routes are possible and inspired by those skilled in the art who have referred to this disclosure.

[0023] The following one or more pharmaceutically acceptable excipients refer to drug-acceptable carriers or excipients, such as those added to conventional diluents (water, etc.), fillers (lactose, etc.), binders (starch, dextrin, etc.), transdermal absorption enhancers, flavoring agents, thickeners, solvents (ethanol, etc.) and other excipients.

[0024] The following topical preparations include ointments, creams, gels, films, patches, tinctures, and aerosols; the following oral preparations include tablets, granules, capsules, pills, powders, oral liquids, and syrups.

[0025] 1. Tissue specimen

[0026] Frozen tissue: specimens of colorectal cancer surgically removed from patients who underwent two cycles of CAPOX preoperative chemotherapy at the Affiliated Hospital of Jiangnan University.

[0027] The inclusion criteria for pathological sections are: 1. Pathologically confirmed colorectal cancer; 2. Pathological sections are from the primary lesion in the colorectal region.

[0028] The exclusion criteria for pathological sections are: 1. The pathological diagnosis is controversial; 2. The clinical treatment is incomplete.

[0029] Based on the patient's intraoperative condition and imaging examinations, the patient was staging using the TNM method. According to these criteria, a total of 47 stage II-III colorectal cancer tissue specimens were included for mass spectrometry analysis. The specimens were collected into cryovials, rapidly frozen in liquid nitrogen, and then stored at -80°C.

[0030] Non-targeted metabolomics analysis based on LC-MS / MS: Surgical specimens of colorectal cancer from the Department of General Surgery, Affiliated Hospital of Jiangnan University were selected. Frozen samples were transported back to the laboratory at low temperatures using a sampling box and stored at -80℃. Tissue proteins were extracted within 48 hours, followed by non-targeted metabolomics analysis based on LC-MS / MS.

[0031] 2. Colon cancer cell lines

[0032] The human colon cancer cell line HCT116 was obtained from the Central Laboratory of the Fifth People's Hospital Affiliated to Fudan University in Shanghai and purchased from Foleibao Biotechnology Co., Ltd.

[0033] 3. Main reagents and consumables

[0034] Fetal bovine serum and 1640 culture medium were produced by Hyclone.

[0035] 2000×PBS powder was purchased from Biosharp.

[0036] EDTA and EDTA-free trypsin were produced by SolarBio, and Tris-HCl (pH 8.8 and pH 6.8) were from Shanghai Baisai Biotechnology Co., Ltd. Tris base was purchased from Biosharp.

[0037] Glycine and SDS powder were produced by Sigma.

[0038] Methanol, isopropanol, anhydrous ethanol, chloroform, and Tween are produced by Guangdong Provincial Chemical Reagent Engineering Technology Research and Development Center.

[0039] DEPC water is produced by Shanghai Sangon Biotech Co., Ltd.

[0040] DMSO is manufactured by McLean.

[0041] Xylene, sodium citrate buffer, hydrogen peroxide solution, DAB working solution, hematoxylin, hydrochloric acid, and neutral resin were purchased from Guangdong Provincial Chemical Reagent Engineering Technology Research and Development Center.

[0042] Various sizes of cell culture dishes, 6-well plates, 12-well plates, and 96-well plates were manufactured by Corning Incorporated. Cell Counting Kit-8 and CCK-8 reagents for detecting cell proliferation were purchased from Dojin Chemical Co., Ltd., Japan.

[0043] 2.5% crystal violet staining solution was purchased from Beijing Solarbio Co., Ltd. Shanghai Yisheng Biotechnology Co., Ltd. BCA protein concentration assay kit (enhanced version).

[0044] The PAGE gel rapid preparation kit was purchased from Shanghai Yamei Biomedical Technology Co., Ltd. The Reporter Assay System Kit was purchased from Promega Biotechnology Co., Ltd.

[0045] Annexin V-APC / 7-AAD double staining apoptosis detection kit was purchased from Jiangsu Kaiji Biotechnology Co., Ltd. The FITC Annexin V Apoptosis Detection Kit was purchased from BD Biosciences, Inc. (USA). Ribo TM The Fluorescent In Situ Hybridization Kit was purchased from Guangzhou Ruibo Biotechnology Co., Ltd.

[0046] 4. Main Experimental Methods

[0047] Cloning

[0048] (1) Cell pretreatment: First, digest the cells using standard methods, transfer the cell suspension to a 1.5 mEP tube, centrifuge at 900 rpm for 5 min, aspirate and discard the supernatant. Resuspend the cells in complete culture medium and seed 500 transfected cells per well in a 3 cm cell culture dish. Then incubate in an incubator (5% CO2, 37℃) for 10–12 days, keeping the cell culture dish static during the incubation period;

[0049] (2) After 10 to 12 days, observe the cell growth. When the cells grow to a suitable size, they can be processed. Aspirate the culture medium from the culture dish and wash twice with PBS.

[0050] (3) Cell fixation: Add 250 μL of anhydrous methanol solution to a 3 cm cell culture dish and fix for 15 min;

[0051] (4) Remove anhydrous methanol, add 200 μL of ammonium oxalate crystal violet solution to the cells, and let stand at room temperature for 15 min;

[0052] (5) Remove the crystal violet solution, rinse the petri dish with distilled water, or invert the petri dish onto absorbent paper until the water is absorbed.

[0053] (6) Count the cells and perform statistical analysis;

[0054] (7) Taking photos: After staining, gently wash away excess crystal violet solution under tap water, air dry, and take photos with a camera.

[0055] CCK-8 method

[0056] Experimental principle: Based on the Cell Counting Kit-8 (CCK-8) reaction principle, the following operational steps are included:

[0057] (1) First, digest the cells using standard methods, place them in a 1.5 mL sterile EP tube, centrifuge at 850 mpm for 5 min, aspirate and discard the supernatant. Resuspend the cells, count the cells, and seed 2 x 10⁵ cells per well in a clear 96-well plate, with 3-4 replicate wells per group;

[0058] (2) The experimental group was set at three time points: 24h, 48h and 72h, while the blank control group was given an equal amount of culture medium.

[0059] (3) Perform the test every 24 hours. Add 6 μL of CCK-8 solution and 94 μL of serum-free cell culture medium to each well (CCK-8 kit instructions) and incubate in an incubator for 2 hours and 30 minutes.

[0060] (4) The OD (Optical Density) value at a wavelength of 450 nm was detected using an enzyme-linked immunosorbent assay (ELISA) reader;

[0061] Flow cytometry (Apoptosis detection - Annexin V detection kit)

[0062] Specific experimental procedures:

[0063] ① Collect the culture medium into a new labeled test tube, digest it with trypsin and collect the cells from the 6-well or 12-well plate into the same test tube;

[0064] ② Centrifuge at 1,000 rpm for 5 minutes, then discard the supernatant;

[0065] ③ Add 1 mL of pre-cooled PBS and wash twice, then centrifuge at 1,000 rpm for 5 min;

[0066] ④ Add 250 μL of 1x Binding Bufer (diluted with PBS) to suspend the cells;

[0067] ⑤ Add 2.5 μL Annexin V-FITC and 2.5 μL LPI, mix gently, and incubate at room temperature in the dark for 15 min;

[0068] ⑥ Nylon mesh (pore size: 50mm) filters cells in the sample to prevent cell clusters from clogging the machine's pipes.

[0069] Finally: flow cytometry was used to detect and statistically analyze the cell apoptosis rate.

[0070] Precautions:

[0071] A. The first experiment also requires setting up cells stained with PI and Annexin V-FITC to adjust fluorescence compensation;

[0072] B. When digesting and collecting cells, use trypsin without EDTA;

[0073] C. If the cell line is a stable cell line that is positive for green fluorescent protein, the Annexin V-APC and 7-AAD apoptosis detection kit should be used.

[0074] IC 50 experiment

[0075] (1) Seed 8000 cells per well in a 96-well cell culture plate;

[0076] (2) After the cells adhered to the wall, CDDP solutions of different concentrations diluted with complete culture medium were added to culture the cells.

[0077] (3) After culturing for 48 hours with the drug, the CDDP solution was removed and the dead cells were washed with PBS;

[0078] (4) Add 100L of 5% CCK-8 prepared from culture medium (containing 10% FBS) to each well;

[0079] (5) Incubate in an incubator for 2 hours, then aspirate 95 μL of liquid into a 96-well microplate and measure the OD value at 450 nm.

[0080] (6) Plot fitting curves based on the different OD values ​​of different drug concentrations.

[0081] 5. Construction of oxaliplatin-resistant cell lines

[0082] This experiment constructed an oxaliplatin-resistant cell line from HCT116. HCT116 cells were treated with gradient concentrations of oxaliplatin, with the culture medium and chemotherapy drugs changed every other day. The oxaliplatin concentration was increased based on the cell state. Cells were passaged after digestion when the confluence reached approximately 80%. Oxaliplatin stimulation was generally not added on the day of passage, but continued thereafter. Cell oxaliplatin sensitivity was periodically monitored. The oxaliplatin-resistant cell line was successfully constructed when the cell sensitivity to oxaliplatin significantly decreased and stabilized with a statistically significant difference.

[0083] 6. Construction of capecitabine-resistant cell lines

[0084] This experiment constructed a capecitabine-resistant cell line from HCT116. HCT116 cells were treated with gradient concentrations of capecitabine, with the culture medium and chemotherapy drugs changed every other day. The capecitabine concentration was increased based on the cell state. Cells were passaged after digestion when the confluence reached approximately 80%. Generally, capecitabine stimulation was not added on the day of passage, but continued afterward. Cell sensitivity to capecitabine was periodically monitored. The resistant cell line was successfully constructed when the cell sensitivity to capecitabine significantly decreased and stabilized with a statistically significant difference.

[0085] This invention provides the pharmaceutical use of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate choline (1-Palmitoyl-2-oleoyl-sn-glycero-3-PC) to increase the drug sensitivity of colorectal cancer cells to oxaliplatin and capecitabine. Studies using clinical specimens have shown a significant decrease in the expression of the glycerophospholipid 1-Palmitoyl-2-oleoyl-sn-glycero-3-PC in tumor tissues, which is negatively correlated with chemotherapy resistance. The addition of this glycerophospholipid significantly improves the sensitivity of colorectal cancer cells to oxaliplatin and capecitabine.

[0086] In in vitro induced chemotherapy-resistant strains, the results were obtained through CCK8 assay and IC50 assay. 50 Quantitative analysis revealed that the treatment group with added 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate choline (1-Palmitoyl-2-oleoyl-sn-glycero-3-PC) exhibited lower cell viability and significantly reduced cell survival rate, demonstrating its ability to enhance the efficacy of chemotherapeutic drugs. Furthermore, flow cytometry apoptosis assays also showed that the addition of this glycerophospholipid increased the apoptosis rate of drug-resistant cell lines, further confirming its role in reversing chemotherapeutic resistance.

[0087] This invention provides an innovative use of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate choline (1-Palmitoyl-2-oleoyl-sn-glycero-3-PC) as a drug sensitivity enhancer in neoadjuvant therapy for colorectal cancer. This technology not only provides new theoretical basis for improving the drug sensitivity of colorectal cancer patients to oxaliplatin and capecitabine, but also provides potential drug targets and treatment strategies for future colorectal cancer treatment.

[0088] To further investigate whether 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate choline (1-Palmitoyl-2-oleoyl-sn-glycero-3-PC) is a tissue-specific glycerophospholipid that can sensitize oxaliplatin and capecitabine, the inventors used two different glycerophospholipids screened by metabolomics that were significantly downregulated in tumor tissues of patients resistant to chemotherapy drugs: glycerophospholipid PC (18:0 / 0:0) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate choline (1-Palmitoyl-2-oleoyl-sn-glycero-3-PC, POPC).

[0089] Figure 1A shows the difference in glycerophospholipid PC (18:0 / 0:0) expression levels between colorectal cancer tumor tissues and paired adjacent normal tissues in this study group, as detected by mass spectrometry; Figure 1B shows the difference in glycerophospholipid 1-Palmitoyl-2-oleoyl-sn-glycero-3-PC (POPC) expression levels between colorectal cancer tumor tissues and paired adjacent normal tissues in this study group, as detected by mass spectrometry. Neoadjuvant chemotherapy regimen CAPOX: patients received chemotherapy with oxaliplatin and capecitabine before surgery; only significantly different glycerophospholipid levels are shown in the figure (P<0.005). Continuous horizontal bars in the figure represent medians. Results are expressed as SEM ± mean.

[0090] CCK8 cell viability assays and IC50 cell survival rate assays revealed that after 24 hours of treatment with 10 μg / ml oxaliplatin or capecitabine, the viability and survival rate of cells in the POPC-treated group did not show a significant decrease (Figure 2, A and B). Furthermore, in the oleophospholipid PC (18:0 / 0:0) treatment group, the viability and survival rate of cells in the oleophospholipid PC (18:0 / 0:0) treatment group did not show a significant change. However, after 48 hours of treatment with 10 μg / ml oxaliplatin or capecitabine, the viability and survival rate of cells in the POPC-treated group significantly decreased (Figure 2, A and B). In the oleophospholipid PC (18:0 / 0:0) treatment group, the viability and survival rate of cells in the oleophospholipid PC (18:0 / 0:0) treatment group did not show a significant change (Figure 2, E). This indicates that glycerophospholipid POPC can significantly exacerbate the proliferation inhibition of HCT116 cells in response to oxaliplatin or capecitabine stimulation.

[0091] The inventors further used flow cytometry to detect HCT116 cell apoptosis and found that the proportion of HCT116 cells in the glycerophospholipid POPC treatment group increased significantly in response to Oxaliplatin or Capecitabine stimulation (AD in Figure 3); and the colony formation experiment also showed that colony formation was significantly reduced in the glycerophospholipid POPC treatment group in response to Oxaliplatin or Capecitabine stimulation (EH in Figure 3), indicating that glycerophospholipid POPC can enhance the chemosensitivity of HCT116 cells and can be used as a chemosensitizer.

[0092] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any form or substance. It should be noted that those skilled in the art can make various improvements and additions without departing from the method of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention. Any modifications, alterations, and equivalent changes made by those skilled in the art based on the above-disclosed technical content without departing from the spirit and scope of the present invention are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, and evolutions made to the above embodiments based on the essential technology of the present invention still fall within the scope of the technical solution of the present invention.

Claims

The use of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline in the preparation of sensitizers for colorectal cancer chemotherapy drugs. Use according to claim 1, characterized in that: The chemotherapy drugs for colorectal cancer are oxaliplatin and / or capecitabine. A colorectal cancer chemotherapeutic drug sensitizer, characterized in that: It includes at least 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine. The colorectal cancer chemotherapeutic drug sensitizer according to claim 3, characterized in that: The colorectal cancer chemotherapy drug sensitizer is an oxaliplatin sensitizer and / or a capecitabine sensitizer. 1-Palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline is used in the preparation of drugs to increase the sensitivity of colorectal cancer patients to oxaliplatin and / or capecitabine. Use of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline for increasing the sensitivity of colorectal cancer cells to oxaliplatin and / or capecitabine. Use according to claim 6, characterized in that: By modulating the function of colon cancer cell membranes with 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline, the sensitivity of colon cancer cells to oxaliplatin and / or capecitabine is enhanced.

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