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Method for improving curative effect of temozolomide in glioblastoma

A technology for glioblastoma and temozolomide, which is applied in the field of improving the efficacy of glioblastoma temozolomide, and can solve problems such as complex mechanisms

Pending Publication Date: 2021-09-10
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the problem of temozolomide drug resistance is common in clinical practice and the mechanism is very complicated. The biggest problem limiting its effect is its drug resistance

Method used

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  • Method for improving curative effect of temozolomide in glioblastoma
  • Method for improving curative effect of temozolomide in glioblastoma
  • Method for improving curative effect of temozolomide in glioblastoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] An interference plasmid for knocking down the expression of COPS5 protein in glioblastoma cell lines, the gene sequence is CCAGACTATTCCACTTAATTT. COPS5: Photogenerating factor 9 complex subunit 5 protein.

[0034] In the study, it was found that the photogenetic factor 9 complex subunit 5 (COPS5) protein was expressed in glioblastoma, and was involved in regulating the ferroptosis process of glioblastoma cells, thereby affecting the drug resistance of temozolomide in treatment.

[0035] The COPS5 expression interference plasmid is specifically an shRNA (short hairpin RNA) plasmid, which is to clone two short inverted repeat sequences specifically targeting the COPS5 gene into the expression vector plasmid, and cause the degradation of the mRNA transcribed by COPS5 after transfection into the cell, and then Interfering with the expression of the COPS5 gene reduces the level of COPS5 protein in cells. This interference plasmid is specially designed for the COPS5 gene, an...

Embodiment 2

[0044] The use of the interfering plasmid used in Example 1 for knocking down the expression of COPS5 protein in glioblastoma cell lines as a drug to solve the drug resistance problem of temozolomide in treatment.

[0045] Knockdown of COPS5 expression combined with temozolomide treatment, compared with knockdown of COPS5 expression alone and temozolomide treatment alone, combined treatment has a better effect on inhibiting the growth of glioblastoma. Such as Figure 8 As shown, compared with the control group, compared with the group using the interference plasmid shCOPS5 alone and the group using temozolomide alone, the combined application of the COPS5 interference plasmid COPS5 and temozolomide had smaller subcutaneous tumor volume in nude mice.

[0046] The interfering plasmid used for knocking down the expression of COPS5 protein in glioblastoma cell lines of the present invention can achieve a more obvious tumor inhibitory growth effect by promoting glioblastoma cell fe...

Embodiment 3

[0048] Provided is a use of a combination drug composed of an interference plasmid for knocking down COPS5 protein expression combined with temozolomide as a chemotherapeutic drug for glioblastoma.

[0049] Knockdown of COPS5 combined with temozolomide can achieve a more significant tumor-inhibitory growth effect by promoting ferroptosis in glioblastoma cells and reducing temozolomide resistance. It can be used as a new drug to improve the efficacy of temozolomide in glioblastoma.

[0050] Such as Figure 9 As shown, in the subcutaneous tumor formation experiment of nude mice, compared with the control group, the volume and weight of subcutaneous tumors in nude mice were significantly reduced after treatment with the COPS5 interference plasmid shCOPS5 and temozolomide, and this trend was even more pronounced under the action of the ferroptosis agonist Erastin. Obviously, it disappeared under the action of ferroptosis inhibitor Erastin-Fer-1.

[0051] It can be seen that the ...

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Abstract

The invention relates to an interference plasmid for knocking down expression of COPS5 protein in a glioblastoma cell line, application of the interference plasmid as a drug for solving the drug resistance problem of temozolomide in treatment, and application of a combined drug formed by the interference plasmid for knocking down expression of the COPS5 protein and temozolomide as a glioblastoma chemotherapeutics. The interference plasmids knock down expression of COPS5 protein and regulate the ferroptosis process of glioblastoma cells, specifically, the expression of ferroptosis promoting protein is increased, and the expression of ferroptosis inhibiting protein is reduced.

Description

technical field [0001] The present invention relates to the technical field of biomedicine, in particular to an interfering plasmid for knocking down the expression of COPS5 protein in glioblastoma cell lines and its use as a drug for solving the drug resistance problem of temozolomide in treatment, As well as the use of a combined drug consisting of an interfering plasmid knocking down COPS5 protein expression combined with temozolomide as a chemotherapy drug for glioblastoma. Background technique [0002] Glioma is the most common primary intracranial tumor, and glioblastoma accounts for about 50% of all gliomas. Glioblastoma is highly aggressive, easy to relapse, and has a high rate of death and disability. Its 5-year overall survival rate is one of the worst among all human cancers. Despite aggressive treatment, the median survival is approximately 15 months. [0003] Temozolomide is an oral alkylating agent antineoplastic drug, which has broad-spectrum antitumor activ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/85C12N15/113A61K31/7088A61K31/4188A61P35/00
CPCC12N15/85C12N15/113C12N15/111A61K31/7088A61K31/4188A61P35/00C12N2800/107C12N2310/14C12N2320/32A61K2300/00
Inventor 赵亮潘志华林婉蝶方俊博
Owner SOUTHERN MEDICAL UNIVERSITY
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