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Application of thbs1 and its inhibitors in the preparation of antitumor drugs

A technology of anti-tumor drugs and inhibitors, which is applied in the field of anti-tumor treatment, and can solve the problems of immature, undiscovered, and less anti-tumor research on Thbs1

Active Publication Date: 2022-06-17
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although many preclinical studies and discoveries have reported that Thbs1 achieves anti-tumor effects through anti-angiogenesis, but no report has been found to achieve immunotherapy for tumors by inhibiting the expression of Thbs1.
All in all, anti-tumor research on Thbs1 is less and immature

Method used

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  • Application of thbs1 and its inhibitors in the preparation of antitumor drugs
  • Application of thbs1 and its inhibitors in the preparation of antitumor drugs
  • Application of thbs1 and its inhibitors in the preparation of antitumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] According to the nucleotide sequence of the Thbs1 protein gene, three siRNAs and shRNAs with interfering sequences were designed and synthesized, namely shRNA1, shRNA2, and shRNA3, which interfered with B16F10 cells in vitro, and extracted total intracellular RNA. Further, the constructed Thbs1 was verified by in vitro qPCR. Interfering effects of interfering sequences. Further experiments were carried out by encapsulating the corresponding shRNA with adenovirus.

[0060] (See Xu, S., Yu, J., Shi, Q., Niu, Q., Guo, Z., Guo, B., Zhou, G., Gu, X., Wu, Y. "Conditionally Replicative adenovirus carrying shRNA targeting EZH2 inhibits prostate cancer growth and invasion". Oncology Reports 42.1(2019):273-282.)

[0061] The C57BL / 6 mouse melanoma model was constructed. After the model was formed, PBS, control virus, adenovirus-encapsulated Thbs1 interfering shRNA, and PBS were injected intratumorally. Three days later, tail vein injection was started. Correspondingly, the tail ...

Embodiment 2

[0071] The C57BL / 6 mouse melanoma model was constructed. After the model was formed, PBS and PBS were injected intratumorally, control virus, adenovirus-encapsulated Thbs1 interfering shRNA#1, and adenovirus-encapsulated Thbs1 interfering shRNA#2, three days later, the tail was started. Intravenous injection, correspondingly, saline, HNPs, HNPs, HNPs, and HNPs were injected into the tail vein, respectively. The HNPs-injected group was given hyperthermia at 42°C for 1 h after injection (HT, Heat treatment). It was administered once every three days, for a total of five doses. The tumor size of mice was measured and recorded before each administration, and intratumoral injection was performed again after the third administration to maintain the effective interference state of Thbs1. After the administration, the lymphocytes of the tumor were extracted and separated, and the content and expression of various lymphocytes were analyzed by flow cytometry.

[0072] Among them, the ...

Embodiment 3

[0085] The GEPIA database was used to analyze the relationship between Thbs1 expression and overall survival curve in adrenocortical carcinoma.

[0086] like Figure 4 As shown, the results show that low Thbs1 expression can significantly prolong survival.

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Abstract

The invention relates to the field of biomedicine, and discloses the application of Thbs1 and its inhibitors in the preparation of antitumor drugs. The present invention provides a therapeutic strategy for targeting Thbs1 to activate the body's immunity to play an anti-tumor effect. Experiments have proved that by inhibiting the expression of Thbs1 at the tumor site, it can promote the body's immunity and effectively inhibit tumor growth. Through the combined use of Thbs1 inhibitors and immune checkpoint inhibitors, the secretion of Thbs1 protein can be inhibited, thereby strengthening chemoimmunotherapy and effectively inhibiting tumor growth. Therefore, the Thbs1 inhibitor disclosed in the present invention can be used as an anti-tumor drug, and can play a role in activating tumor immunotherapy, and has important application value.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to drugs, inhibitors and treatment methods targeting thrombospondin (Thrombospondin-1, Thbs1), and their application in the field of anti-tumor treatment. Background technique [0002] According to the latest report from the American Cancer Society in 2019, over the past decade, the incidence of cancer in women in the United States has stabilized, the incidence of cancer in men has decreased by about 2% per year, and the cancer mortality rate (2007-2016) has decreased each year respectively 1.4% and 1.8%, all of which are undoubtedly attributed to the development and progress of various anti-tumor therapies. In China, there were 4.3 million new cancer cases and 2.9 million new cancer deaths in China in 2018. Compared with the United States and the United Kingdom, China has a lower incidence of cancer, but the cancer death rate is 30% and 40% higher than that of the United Kingdom and the...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/713A61P35/00A61P35/02
CPCA61K45/00A61K31/713A61P35/00A61P35/02
Inventor 何伟夏元铮肖青青李晓彤
Owner CHINA PHARM UNIV
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