CN-121287749-B - Use of GABAA alpha 6 receptor knockout substance and its combination in preparation of products for treating bladder cancer

Abstract

The invention discloses a GABAA alpha 6 receptor knockout substance and application of a combination medicament thereof in preparing a product for treating bladder cancer. The invention provides an application of a substance for knocking out GABAA alpha 6 receptor genes and a macrophage inhibitory drug in preparing a tumor treatment product. Also provided are the use of a GABAA α6 receptor gene knockout substance and a macrophage inhibitory drug in the preparation of a product for inhibiting tumor progression. The invention researches the regulation and control effect of GABAA alpha 6 receptor gene on CD8+T cell function by knocking out the GABAA alpha 6 receptor gene, and verifies the application value of the GABAA alpha 6 receptor gene in bladder cancer treatment, thereby providing a new strategy for clinical treatment.

Inventors

• FAN WENMEI
• JIANG HAOWEN
• ZHAO XUPENG
• Cao Senming
• FENG YI

Assignees

• 中国人民解放军总医院第三医学中心

Dates

Publication Date

20260508

Application Date

20251210

Claims (4)

1. 1. Use of a GABAA α6 receptor gene knockout substance and a macrophage inhibitory drug in the preparation of a product for the treatment of bladder cancer; The substances for knocking out the GABAA alpha 6 receptor gene are cas protein and gRNA; the macrophage inhibitory drug is a chlorophosphonate liposome.
2. 2. Use of a GABAA α6 receptor gene knockout substance and a macrophage inhibitory drug in the preparation of a product for inhibiting progression of bladder cancer; The substances for knocking out the GABAA alpha 6 receptor gene are cas protein and gRNA; the macrophage inhibitory drug is a chlorophosphonate liposome.
3. 3. A product for treating bladder cancer comprising a GABAA α6 receptor gene knockout substance, a macrophage inhibitory drug, and a pharmaceutically acceptable carrier; The substances for knocking out the GABAA alpha 6 receptor gene are cas protein and gRNA; the macrophage inhibitory drug is a chlorophosphonate liposome.
4. 4. A product for inhibiting progression of bladder cancer comprising a GABAA α6 receptor gene knockout substance, a macrophage inhibitory drug, and a pharmaceutically acceptable carrier; The substances for knocking out the GABAA alpha 6 receptor gene are cas protein and gRNA; the macrophage inhibitory drug is a chlorophosphonate liposome.

Description

Use of GABAA alpha 6 receptor knockout substance and its combination in preparation of products for treating bladder cancer Technical Field The invention belongs to the technical field of biology, and relates to an application of a GABAA alpha 6 receptor knockout substance and a combined medicament thereof in preparing a product for treating bladder cancer. Background Bladder cancer is a worldwide common malignancy of the urogenital system with high morbidity and mortality. At present, the clinical treatment mainly comprises surgical excision, BCG infusion and chemotherapy, but has the problems of large wound, high recurrence rate, drug resistance and the like. Therefore, the development of novel immunotherapeutic approaches is an important direction for the treatment of bladder cancer. Cd8+ T cells are core killer cells in tumor immunity and induce apoptosis of tumor cells by secreting cytokines (e.g., TNF- α, IFN- γ) and cytotoxic molecules (e.g., granzyme B, perforin). However, tumor microenvironments often inhibit cd8+ T cell function, resulting in reduced killing capacity. It was found that gamma-aminobutyric acid (GABA) and its receptors (e.g., GABAA receptor) can regulate immune cell function, wherein GABAA α6 receptor is specifically and highly expressed in activated cd8+ T cells, but the effect of the receptor on cd8+ T cell killing function and bladder cancer progression is not yet clear. Disclosure of Invention The technical problem solved by the invention is how to improve the killing power of CD8+ T cells and how to treat tumors such as bladder cancer. To solve the above technical problems, the first aspect of the present invention provides the use of a substance for knocking out GABAA α6 receptor gene and a macrophage inhibitory drug for preparing a product for treating tumor. In a second aspect, the invention provides the use of a substance for knocking out the GABAA α6 receptor gene and a macrophage inhibitory drug in the preparation of a product for inhibiting tumor progression. In a third aspect, the invention provides a product for the treatment of a tumor comprising a substance that knocks out the GABAA α6 receptor gene, a macrophage inhibitory drug, and a pharmaceutically acceptable carrier. In a fourth aspect, the invention provides a product for inhibiting tumor progression comprising a substance that knocks out the GABAA α6 receptor gene, a macrophage inhibitory drug, and a pharmaceutically acceptable carrier. In a fifth aspect, the invention provides the use of a substance for knocking out the GABAA α6 receptor gene for the preparation of any one of the following products: a1 Increasing the killing capacity of cd8+ T cells against tumor cells; A2 Enhancement of cd8+ T cell activation; A3 Leading to cycle arrest of tumor cells; A4 Promoting apoptosis of tumor cells; A5 Promoting secretion of TNF- α and/or GZMB cytokines by tumor cells; A6 Inhibit disease progression due to reduced cd8+ T cell function. In a sixth aspect, the invention provides the use of cd8+ T cells knocked out of the GABAA α6 receptor gene for the preparation of any one of the following products: B1 Improving the killing capacity against tumor cells; b2 Enhancement of cd8+ T cell activation; b3 Leading to tumor cell cycle arrest; b4 Promoting apoptosis of tumor cells; b5 Promoting secretion of TNF- α and/or GZMB cytokines by tumor cells; B6 Inhibit disease progression due to reduced cd8+ T cell function. In a seventh aspect, the invention provides a product comprising a substance that knocks out the GABAA α6 receptor gene or cd8+ T cells that knocks out the GABAA α6 receptor gene, and a pharmaceutically acceptable carrier. The product described above has any of the following functions: a1 Increasing the killing capacity of cd8+ T cells against tumor cells; A2 Enhancement of cd8+ T cell activation; A3 Leading to cycle arrest of tumor cells; A4 Promoting apoptosis of tumor cells; A5 Promoting secretion of TNF- α and/or GZMB cytokines by tumor cells; A6 Inhibit disease progression due to reduced cd8+ T cell function. In an eighth aspect, the present invention provides an application of a GABAA α6 receptor gene knockout substance in developing and researching a tumor drug; Or, the invention provides the application of the substance for knocking out the GABAA alpha 6 receptor gene in preparing and developing tumor drug models; or, the invention provides the application of GABAA alpha 6 receptor or gene thereof or expression cassette containing the gene, and recombinant vector in preparing the product for inhibiting the progress of tumor. In the above, the tumor is bladder cancer. In certain embodiments, the substance that knocks out the GABAA α6 receptor gene may be a substance that knocks out the GABAA α6 receptor gene in a cell. In certain embodiments, the substance that knocks out the GABAA α6 receptor gene in the cell may be a substance that knocks out the GABAA α6 receptor gene in a cd8+ cell. In certain embodiment