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Method for enhancing anti-cervical cancer activity of glutaminase enzyme inhibitor by taking TIGA1 (Transcript Induced by Growth Arrest 1) as target spot

A glutaminase and inhibitor technology, applied in the directions of organic active ingredients, anti-tumor drugs, pharmaceutical formulations, etc., can solve the problems of limited anti-tumor effect and large side effects

Active Publication Date: 2017-05-17
SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, glutaminase inhibitors have relatively large side effects and their antitumor effects are relatively limited, which is related to the drug resistance produced by the Warburg effect of cancer cells.

Method used

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  • Method for enhancing anti-cervical cancer activity of glutaminase enzyme inhibitor by taking TIGA1 (Transcript Induced by Growth Arrest 1) as target spot
  • Method for enhancing anti-cervical cancer activity of glutaminase enzyme inhibitor by taking TIGA1 (Transcript Induced by Growth Arrest 1) as target spot
  • Method for enhancing anti-cervical cancer activity of glutaminase enzyme inhibitor by taking TIGA1 (Transcript Induced by Growth Arrest 1) as target spot

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1, TIGA1 expression in silenced tumor cells

[0039] In long-term experiments, it was found that the TIGA1 gene is closely related to the Warburg effect and energy metabolism of cancer cells. At the same time, it was found that the efficacy of glutaminase inhibitors as anti-tumor drugs is not ideal, and the low efficacy of this drug may be related to the Warburg effect. Therefore, to study whether TIGA1 as a target can improve the anti-tumor effect of glutaminase inhibitors.

[0040] 1. Transient transfection of siRNA into Hela cells

[0041] 1. Two siRNAs used to interfere with TIGA1 gene expression

[0042] siTIGA1-1:

[0043] Sense strand 5'-GGAUGUCCUUGGUGAGGAUTT-3' (SEQ ID NO: 1),

[0044] Antisense strand 5'-AUCCUCACCAAGGACAUCCTT-3' (SEQ ID NO: 2);

[0045] siTIGA1-2:

[0046] Sense strand 5'-GGCCUUACCGUAUAACUGATT-3'

[0047] Antisense strand 5'-UCAGUUAUACGGUAAGGCCTT-3'.

[0048] 2'methoxy groups are used on the U and C bases on the siRNA duplex;

...

Embodiment 2

[0064] Example 2. Application of Silencing TIGA1 Expression in Tumor Cells in Treating Tumors

[0065] 1. In vitro soft agar colony formation

[0066] The siTIGA1-1 cells (SHTIGA1) and GV248 vector cells (SHNC) in the logarithmic growth phase were collected respectively, and the cell concentration was adjusted to prepare a cell suspension of 500 viable cells per milliliter. Add 9ml of this cell suspension to the 15ml EP tube, then add 1ml of 3% agar and mix well. Add 2ml of the mixed liquid to each well of the six-well plate, and let it stand at room temperature for 20 minutes to solidify. Cells were cultured in a carbon dioxide incubator at 37°C.

[0067] The above cells were divided into control group and experimental group for treatment respectively:

[0068] Control group: each cell was cultured in a medium containing DMSO for 10 days, and a fresh medium was replaced every 3 days;

[0069] The medium containing DMSO consists of DMSO (D2650) and cell culture medium. Th...

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Abstract

The invention discloses a method for enhancing the anti-cervical cancer activity of glutaminase enzyme inhibitor by taking TIGA1 (Transcript Induced by Growth Arrest 1) as a target spot, and provides application of a substance for inhibiting or reducing TIGA1 expression in tumor cells in preparing a product for treating tumor, or the application of the substance for inhibiting or reducing the TIGA1 expression in the tumor cells in preparing a product for inhibiting tumor cell growth. According to the method disclosed by the invention, an experiment verifies that by using a TIGA1 gene as an effective target spot and combining an RNA (Ribonucleic Acid) interference technology and the glutaminase enzyme inhibitor, the drug resistance of cancer cells is remarkably reduced, and the anti-cancer activity of the glutaminase enzyme inhibitor is increased the method can be used for treating cervical cancer. Combination of the target spots and chemotherapy drugs such as the glutaminase enzyme inhibitor may be a means for increasing the curative effect of the chemotherapy drugs and reducing the death rate of the cervical cancer, and the anti-tumor effect of the glutaminase enzyme inhibitor is greatly increased.

Description

technical field [0001] The present invention relates to the field of biotechnology, in particular to a method for using TIGA1 (Transcript Induced by Growth Arrest 1) as a target to enhance the anticancer activity of glutaminase inhibitors to effectively treat cervical cancer and other cancers. Background technique [0002] Cervical cancer is usually a disease that is difficult to treat with chemotherapy drugs. The vast majority of cervical cancers contain immune human papillomavirus (HPV) antigens. Statistics from the World Health Organization show that cervical cancer ranks second in cancer mortality among women in the world. About 466,000 women are diagnosed with cervical cancer each year, and about 288,000 patients die. There are about 135,000 new cases of cervical cancer in my country every year, and about 30,000 to 50,000 deaths. [0003] The carbon and nitrogen sources of cancer cell metabolism mainly come from glucose and glutamine. Even in the presence of oxygen, ...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/713A61P35/00
CPCA61K31/713A61K45/00
Inventor 孙兵张雅鸥廖梅坚廖卫捷张世宽张佩琢卢锦华
Owner SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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