Application of mevalonic acid metabolism pathway inhibitor and alphavirus in preparing antitumor drug

A technology of mevalonate and inhibitor, applied in the field of biomedicine, can solve problems such as unclear mechanism of action

Active Publication Date: 2019-07-09
GUANGZHOU VIROTECH PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the patent 201510990705.7 previously applied by the inventor, chrysophanol and its derivatives are used as anti-tumor synergists of oncolytic viruses. The combination of the two can reduce the ...

Method used

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  • Application of mevalonic acid metabolism pathway inhibitor and alphavirus in preparing antitumor drug
  • Application of mevalonic acid metabolism pathway inhibitor and alphavirus in preparing antitumor drug
  • Application of mevalonic acid metabolism pathway inhibitor and alphavirus in preparing antitumor drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0128] Example 1 siRNA targeting 3-hydroxy-3-methylglutaryl-CoA reductase HMGCR and M1 virus significantly increased the morphological lesions of human intestinal cancer and pancreatic cancer cell lines.

[0129] Material:

[0130] Human intestinal cell carcinoma HCT-116 (purchased from the Cell Bank of the Chinese Academy of Sciences), human pancreatic cell carcinoma Capan-1 (purchased from ATCC), SW1990 (purchased from ATCC), M1 virus (preservation number CCTCC V201423), high-glucose DMEM medium (purchased from Corning), inverted phase contrast microscope.

[0131] method:

[0132] Cells were seeded in a 35mm culture dish, and the following interference treatment was performed when the cell confluence reached 60%; first, Lipofectamine RNAiMAX solution was prepared with optimized medium (Opti-MEM), diluted according to 2 μL per culture dish: 198 μL, and mixed; Secondly, prepare the siRNA solution with the optimized medium (Opti-MEM), dilute it according to 1.8μL:198μL per c...

Embodiment 2

[0137] Example 2 Combined treatment of siRNA targeting 3-hydroxy-3-methylglutaryl-CoA reductase HMGCR with M1 virus significantly reduced the survival rate of human intestinal cell carcinoma lines.

[0138] Material:

[0139] Human intestinal cell carcinoma HCT-116 (purchased from the Cell Bank of the Chinese Academy of Sciences), M1 virus (preservation number CCTCCV201423), high-glucose DMEM medium (purchased from Corning).

[0140] method:

[0141] a) Cell culture: human intestinal cell carcinoma HCT-116 was grown in DMEM complete medium containing 10% FBS, 100U / ml penicillin and 0.1mg / ml streptomycin; all cell lines were placed in 5% CO 2 , cultured and subcultured in a closed incubator with a constant temperature of 37°C (95% relative humidity), and observed the growth with an inverted microscope. The cells were subcultured every 2-3 days, and the cells in the logarithmic growth phase were taken for formal experiments.

[0142] b) Cells were seeded in a 24-well plate, 3...

Embodiment 3

[0147] Example 3 Statins and M1 virus significantly increased the morphological lesions of human intestinal cell carcinoma lines and promoted the replication of M1 virus. Material:

[0148] Human intestinal cell carcinoma HCT-116 (purchased from the Cell Bank of the Chinese Academy of Sciences), M1 virus (preservation number CCTCCV201423), high-glucose DMEM medium (purchased from Corning), and an inverted phase-contrast microscope.

[0149] method:

[0150] a) Cell culture: human intestinal cell carcinoma HCT-116 was grown in DMEM complete medium containing 10% FBS, 100U / ml penicillin and 0.1mg / ml streptomycin; all cell lines were placed in 5% CO 2 , cultured and subcultured in a closed incubator with a constant temperature of 37°C (95% relative humidity), and observed the growth with an inverted microscope. The cells were subcultured every 2-3 days, and the cells in the logarithmic growth phase were taken for formal experiments.

[0151] b) Cell treatment and morphological...

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PUM

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Abstract

The invention belongs to the field of biomedicine and relates to application of a mevalonic acid metabolism pathway inhibitor and alphavirus in preparing antitumor drug. The invention finds for the first time that the mevalonic acid metabolism pathway inhibitor can be used for preparing an alphavirus antitumor synergist. The invention further relates to a drug composition and a drug set which respectively contain the mevalonic acid metabolism pathway inhibitor and the alphavirus and application of the inhibitor and the alphavirus in treating tumor, especially for tumor insensitive to the alphavirus.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to the application of the combination of mevalonate metabolic pathway inhibitors and alphaviruses in the preparation of antitumor drugs. Background technique [0002] Oncolytic virus is a kind of replication-competent virus that selectively infects and kills tumor cells without damaging normal cells. Oncolytic virus therapy (oncolytic virotherapy) is an innovative tumor-targeted treatment strategy, which uses natural or genetically engineered viruses to selectively infect tumor cells and replicate in tumor cells to achieve targeted dissolution, The effect of killing tumor cells, but no damage to normal cells. [0003] M1 virus (Alphavirus M1) belongs to the genus Alphavirus (Alphavirus). The M1 virus can selectively cause the death of tumor cells without affecting the survival of normal cells, and it has a very good application prospect in anti-tumor. However, different tumors have differ...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61P35/00
CPCA61K45/06A61K35/768A61K2300/00A61P35/00A61K31/404A61K31/40A61K31/4709A61K31/216A61K31/713C12N7/00C12N2770/36132
Inventor 颜光美梁剑开朱文博张海鹏林园蔡静龚守芳
Owner GUANGZHOU VIROTECH PHARMA
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