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Application of small molecular compound YJ-5-41 to preparation of anti-gastric cancer drugs

A compound and gastric cancer technology, applied in the field of medicine, can solve problems such as toxicity, restricting the use of anticancer drugs, and increasing cardiovascular risk

Inactive Publication Date: 2021-08-31
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, long-term use of COX-2 inhibitors can easily cause renal and gastrointestinal toxicity and increase cardiovascular risk
These factors limit its use as an anticancer drug

Method used

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  • Application of small molecular compound YJ-5-41 to preparation of anti-gastric cancer drugs
  • Application of small molecular compound YJ-5-41 to preparation of anti-gastric cancer drugs
  • Application of small molecular compound YJ-5-41 to preparation of anti-gastric cancer drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Cytotoxicity evaluation of formula (I) YJ-5-41.

[0032] 1. Cell culture

[0033] Human gastric cancer cell lines BGC-823, MGC-803, HGC-27, MKN45, AGS and SGC-7901, mouse gastric cancer cell line MFC, and human gastric mucosal epithelial cells GES-1 were all cultured in 10% fetal bovine serum In 1640 medium, the concentration of penicillin-streptomycin was 1%. The cells were cultured in a constant temperature incubator at 37°C (humidity 95%, carbon dioxide concentration 5%).

[0034] 2. MTS assay for cell proliferation

[0035] Cells in the logarithmic growth phase were seeded into 96-well plates at a cell density of 2.5-10×10 3 100 μl medium per well. After 12 hours, different concentrations of YJ-5-41 (administration group) or E7046 (positive group) were added, and the same amount of 1640 complete medium was added to the control group, and three replicate wells were set up in each group. After continuing to culture for 72 hours, 20 microliters of MTS w...

Embodiment 2

[0040] Example 2: Formula (I) YJ-5-41 significantly promotes the differentiation of mouse bone marrow cells into dendritic cells (DC).

[0041] 1. Dendritic cell formation experiment

[0042] Bone marrow cell preparation:

[0043] 615 mice aged 8 to 10 weeks were anesthetized and killed. After being sterilized by 75% ethanol, the femur and tibia of the mouse were taken out, the two ends of the bone were cut off, the bone marrow cells were blown out, centrifuged at 1500 rpm for 5 minutes, the supernatant was discarded and lysed. Red blood cells, 1500 rpm, centrifuge for 5 minutes, discard the supernatant, resuspend the cells and count, adjust the cell density to 3.0×10 6 cells / ml, spread on a 6-well plate.

[0044] Experimental group:

[0045] The blank group only added cytokines: granulocyte-macrophage colony-stimulating factor (GM-CSF, 10 ng / ml) and interleukin 4 (IL-4, 5 ng / ml);

[0046] The control group added the above cytokines and prostaglandin E 2 (10 namos);

[0...

Embodiment 3

[0052] Embodiment 3: Formula (I) YJ-5-41 inhibits prostaglandin E 2 (PGE 2 )-induced granulocyte-like-myeloid-derived immunosuppressive cells (Gr-MDSC) formation.

[0053] Technical method:

[0054] 1. Granulocytoid-bone marrow-derived immunosuppressive cell formation experiment

[0055] Bone marrow cell preparation:

[0056] 615 mice aged 8 to 10 weeks were anesthetized and killed. After being sterilized by 75% ethanol, the femur and tibia of the mouse were taken out, the two ends of the bone were cut off, the bone marrow cells were blown out, centrifuged at 1500 rpm for 5 minutes, the supernatant was discarded and lysed. Red blood cells were centrifuged at 1500 rpm for 5 minutes, the supernatant was discarded, the cells were resuspended and counted, and the cell density was adjusted to 1.5×10 6 cells / ml, spread on a 12-well plate.

[0057] Experimental group:

[0058] The blank group only added cytokines: granulocyte-macrophage colony-stimulating factor (GM-CSF, 40 ng / ...

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Abstract

The invention provides an application of YJ-5-41 of formula (I) to preparation of anti-gastric cancer drugs, and reveals that a compound plays an immune regulation function in vitro and in vivo so as to inhibit growth of gastric cancer. In vitro, the compound can promote formation of dendritic cells (DC), inhibit the formation of granulocyte-like bone marrow-derived immunosuppressive cells (Gr-MDSC), and inhibit the expression of immunosuppressive factor arginase 1 (Arg1) and inducible nitric oxide synthase (iNOS) by the bone marrow-derived immunosuppressive cells (MDSC). In vivo, the compound can inhibit subcutaneous growth of the gastric cancer, obviously promote infiltration of CD8+T cells in tumors, chemotactic factors CXCL10 and CXCL11 recruited by the T cells, obviously promote secretion of cell factors gamma-interferon, tumor necrosis factors and granzyme B which have the effect of tumor killing, obviously promote the proportion of antigen presenting cells, promote polarization of macrophages to M1 type macrophages, can obviously reduce the proportion of the granulocyte-like bone marrow-derived immunosuppressive cells, has an important effect of improving the immunosuppressive microenvironment in gastric cancer tumors, solves the difficult problem of clinical gastric cancer treatment, and has an application prospect in gastric cancer treatment.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of prostaglandin E2 receptor subtype EP4 (EP4 receptor) antagonist YJ-5-41 in treating gastric cancer. Background technique [0002] Gastric cancer originates from the mucosal epithelial cells on the outermost layer of the stomach wall. It is a common malignant tumor of the digestive system. Gastric cancer patients in China account for about 1 / 3 of the global population. The treatment of gastric cancer is still based on radical surgical resection, supplemented by chemotherapy and radiotherapy. Due to the insidious onset and low rate of early diagnosis of gastric cancer, about 40% of patients are already in the advanced stage when diagnosed. Therefore, the low surgical resection rate and low long-term survival rate have become the characteristics of gastric cancer. For patients with unresectable advanced gastric cancer, the main treatment is systemic chemotherapy...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/381A61P35/00
CPCA61K31/381A61P35/00
Inventor 刘明耀胡盼易正芳彭世鸿杨俊杰章涵堃
Owner EAST CHINA NORMAL UNIV
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