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Application of fatty acid oxidation inhibitor in preparing medicine for treating colorectal cancer

A technology for fatty acid oxidation and colorectal cancer, applied in the field of medicine, can solve problems such as unknown effects, and achieve the effect of preventing and reducing the incidence of peritoneal metastasis

Pending Publication Date: 2020-05-05
THE SIXTH AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, whether the lipid metabolism of CAFs in the tumor microenvironment of colorectal cancer is related to the energy metabolism of colorectal cancer cells and whether it plays a role in the peritoneal metastasis of colorectal cancer remains unknown

Method used

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  • Application of fatty acid oxidation inhibitor in preparing medicine for treating colorectal cancer
  • Application of fatty acid oxidation inhibitor in preparing medicine for treating colorectal cancer
  • Application of fatty acid oxidation inhibitor in preparing medicine for treating colorectal cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Specific operation method:

[0040] 1. Tumor tissues from patients with T4 colorectal cancer: all from the Sixth Affiliated Hospital of Sun Yat-sen University.

[0041] Inclusion criteria for the experimental group: ①All patients diagnosed with colorectal tumor and peritoneal metastasis in the colorectal cancer database since the establishment of our hospital; ②Age between 18 and 70 years old; ③T4 patients diagnosed clinically or pathologically; ④adenocarcinoma diagnosed pathologically;

[0042] Exclusion criteria: ①Combined with other organ metastasis (including patients with other organ metastasis within 3 months after operation) ②Patients with familial adenomatous polyposis (FAP) and IBD with cancerous changes ③Combined with other tumors at the same time ④Emergency surgery ⑤Preoperative new surgery Adjuvant therapy or received radiotherapy and chemotherapy due to other diseases ⑥ Combined with perforation before operation ⑦ Multi-source colorectal tumors;

[0043]...

Embodiment 2

[0052] Specific operation method:

[0053] 1. Lipid metabolomics:

[0054] Lipid metabolomics is a research model based on high-throughput analysis technology to systematically analyze the lipid composition and expression changes in organisms. Lipidomics analysis can efficiently study the changes and functions of lipid families and lipid molecules in various biological processes, and then clarify the related biological activity processes and mechanisms. At present, lipidomics analysis generally adopts liquid chromatography-mass spectrometry (LC-MS), which is mainly divided into two types: untargeted or nontargeted and targeted analysis. Among them, the non-targeted analysis mode can realize unbiased and systematic analysis of various types of lipids in the sample, while the targeted analysis mode is mainly for selective and specific quantitative analysis of specific lipid molecules. This project uses a non-targeted lipidomics analysis platform based on UPLC-Orbitrap mass spe...

Embodiment 3

[0082] Specific operation method:

[0083] 1. Transwell detection of metastasis and invasion ability: In Matrigel in vitro invasion experiment, 60-80 μl of diluted Matrigel (DMEM:Matrigel about 10:1 dilution) was added to the polycarbonate membrane (6.5 mm in diameter, 8 μm in diameter) in the upper chamber of Transwell. (Note that the volume should not be too large, it is best to just soak the polycarbonate membrane), and set it at 37°C for 30 minutes to make Matrigel polymerize into a gel. Add various CAFs (2000 / well) in the lower chamber of the Transwell; make a single-cell suspension in the serum-free medium of the cells to be tested, and make three holes for each cell; accurately add 5×10 cells in the upper chamber. 4 cells / well, cell suspension volume 100 μl, placed in 5% CO2 incubator at 37°C for 24h. After the incubation time is over, discard the liquid in the upper chamber, carefully take out the upper chamber, and wipe off the cells on the membrane that have not pen...

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Abstract

The invention discloses application of a fatty acid oxidation inhibitor Etomoxir in preparing a medicine for treating colorectal cancer. Specifically, the fatty acid oxidation inhibitor Etomoxir achieves the purpose of inhabiting peritoneal metastasis of CAFs (cancer-associated fibroblasts)-induced colorectal cancer by inhibiting lipid metabolism of CAFs. According to the application, protein expression in primary tumor tissue with peritoneal metastasis and without peritoneal metastasis of a patient suffering from colorectal cancer is tested through proteomics, and results show that proteins related to lipid metabolism of the primary tumor tissue with peritoneal metastasis, particularly a fatty acid oxidation key enzyme CPT1A, are remarkably reduced. The application makes bases and provides theoretical foundations for prevention and treatment on peritoneal metastasis of colorectal cancer, meanwhile, provides novel treatment ideas for effectively preventing and reducing the occurrence rate of peritoneal metastasis in clinical treatment, and has significant potential application value.

Description

technical field [0001] The invention relates to the technical field of medicine, and relates to the application of fatty acid oxidation inhibitors in the preparation of medicines for treating colorectal cancer. Background technique [0002] Colorectal cancer (CRC), as a common malignant tumor of the digestive tract, is a serious threat to human health. According to the "2018 Global Cancer Statistics", the incidence and mortality of colorectal cancer rank third and second respectively among all malignant tumors, with 1.0966 million new cases and 551,300 deaths. The incidence and mortality of cancer in China rank first in the world, and the incidence and mortality of colorectal cancer rank fourth among all malignant tumors. Common distant metastases of colorectal cancer include liver metastasis, lung metastasis, and peritoneal metastasis, and distant organ metastasis is one of the main causes of death in patients with advanced colorectal cancer. Peritoneal metastasis refers ...

Claims

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Application Information

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IPC IPC(8): A61K31/336A61P35/00A61P35/04
CPCA61K31/336A61P35/00A61P35/04
Inventor 刘晓霞王磊彭绍勇陈代词王辉袁紫旭蔡建黄斌杰
Owner THE SIXTH AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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