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Application of SRCAP ATPase inhibitor in colorectal cancer treatment

A technology of colorectal cancer and inhibitors, applied in the field of application of SRCAP ATPase inhibitors in the treatment of colorectal cancer

Pending Publication Date: 2021-01-05
INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Inhibitory effect of this compound on other ATPase activities, on Lgr5 + Self-renewal of colorectal cancer stem cells and regulation of colorectal cancer have not been reported

Method used

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  • Application of SRCAP ATPase inhibitor in colorectal cancer treatment
  • Application of SRCAP ATPase inhibitor in colorectal cancer treatment
  • Application of SRCAP ATPase inhibitor in colorectal cancer treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1: It is proved that SRCAP can promote the occurrence of colorectal cancer and the self-renewal of intestinal cancer stem cells.

[0049] On the human colorectal cancer tissue chip (purchased from Shanghai Xinchao Biotechnology Co., Ltd., colon cancer 180-point survival tissue chip, product number HColA180Su15), it was observed that SRCAP was lowly expressed in human normal colorectal epithelial cells, while in colorectal cancer It is highly expressed in tumors, and its expression increases continuously with the progress of tumors, such as figure 1 , as shown in A. The expression statistics of SRCAP in different stages and grades of colorectal cancer, such as figure 1 , shown in B. Analysis of SRCAP expression and survival time showed that patients with high SRCAP expression had a poor prognosis in colorectal cancer, such asfigure 1 , as shown in C. On the SRCAP knockdown human colon cancer cell line HCT116 (HCT116 cells were purchased from the Shanghai Cell ...

Embodiment 2

[0050] Example 2: Proving that the SRCAP ATPase inhibitor Amtizole has an inhibitory effect on colorectal cancer caused by the self-renewal of intestinal cancer stem cells.

[0051] The small molecule compound Amtizole significantly inhibited the activity of SRCAP ATPase in the in vitro SRCAP ATPase enzyme activity detection system (reference [2]), as shown in figure 2 , shown in A (at OD 620 Under the colorimetric reading value, IgG was used as a negative control, and the difference between the positive reading value and IgG was used as the relative enzyme activity value, DMSO=0.38±0.04, Amitizole=0.09±0.02). Inhibit the ratio of intestinal cancer stem cells forming organoid CCO (colorectal cancer organoid, human colorectal cancer organoid) in the culture system, such as figure 2 , shown in B. Amtizole (1.5mg / kg body weight) on Apc min Spontaneous colorectal cancer in mice (see [1] for animal model / method references) was significantly inhibited, as figure 2 , as shown ...

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Abstract

The invention provides an application of a reagent for detecting the activity of SRCAP ATPase or the expression level of a downstream transcription factor regulated and controlled by the SRCAP ATPasein preparation of a diagnostic agent / kit for diagnosing or prognosing colorectal cancer diseases of mammals. The invention further provides an application of an inhibitor / antagonist of the activity ofthe SRCAP ATPase or the downstream transcription factor regulated and controlled by the SRCAP ATPase in preparation of a medicine / kit for preventing or treating the colorectal cancer diseases of themammals.

Description

technical field [0001] The invention provides the application of SRCAP ATPase inhibitor to inhibit colorectal cancer stem cells. Background technique [0002] Intestinal epithelial cells cover the entire surface of the intestinal tract and perform many important functions in the body, such as nutrient absorption, mucosal barrier, secretion and immune regulation, and maintain the dynamic balance of the body. The intestinal epithelium is composed of rapidly proliferating intestinal crypts and differentiated villi forming the basic organizational structure. There are crypts composed of intestinal stem cells (intestine stem cells, ISCs), Paneth cells, and proliferating cells, as well as absorptive epithelial cells, cups, and Stem cells, endocrine cells and Tuft cells. Self-renewal and pluripotent differentiation of ISCs under physiological conditions maintain intestinal epithelial homeostasis. Pathological conditions can lead to severe impairment of epithelial function. ISCs ...

Claims

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Application Information

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IPC IPC(8): A61K31/433A61P35/00A61P1/00C12Q1/6886G01N33/574G01N33/68
CPCA61K31/433A61P35/00A61P1/00C12Q1/6886G01N33/6893G01N33/57419G01N33/57446C12Q2600/118
Inventor 范祖森叶步青杨柳柳刘本宇钱国敏杜颖王彦英李慧目
Owner INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES