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New application of acyl coenzyme A/cholesterol acyltransferase-1 inhibitor

A cholesterol acyl and transferase technology, applied in the field of biomedicine, can solve problems such as limited diagnosis and treatment methods

Inactive Publication Date: 2019-01-04
BEIJING PROTEOME RES CENT +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The means of diagnosis and treatment are very limited

Method used

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  • New application of acyl coenzyme A/cholesterol acyltransferase-1 inhibitor
  • New application of acyl coenzyme A/cholesterol acyltransferase-1 inhibitor
  • New application of acyl coenzyme A/cholesterol acyltransferase-1 inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0102] Example 1. The high expression of ACAT1 in liver cancer is closely related to the occurrence and prognosis of liver cancer

[0103] In order to confirm the high expression of ACAT1 in liver cancer, the inventors used the liver cancer tissue chip (95 liver cancer / 85 matching adjacent cancer) to detect the significantly high expression of ACAT1 in HCC ( figure 1 A, B), the overall survival of patients with high expression of ACAT1 was significantly lower than that of patients with low expression of ACAT1 ( figure 1 C). It is confirmed that ACAT1 is closely related to the occurrence and prognosis of liver cancer.

Embodiment 2

[0104] Example 2, the catalyzed product cholesteryl ester of ACAT1 is significantly highly expressed in human liver cancer tissue

[0105] In order to confirm the high expression of ACAT1 in liver cancer, the inventors used mass spectrometry to measure the content of ACAT1 catalytic product cholesteryl ester in 25 pairs of liver cancer and corresponding paracancerous tissues. The results showed that the main catalytic substrate of ACAT1 in cells, the concentration of cholesteryl ester standard (CE 18:1), was significantly higher in HCC than in the paired paracancerous tissues (Fig. 2A); the catalytic product of ACAT1, cholesteryl ester (6 species ) expression difference in human liver cancer (T) compared with paracancerous tissue (NT) ( figure 2 B). It further proved that the expression of its catalytic enzyme ACAT1 in liver cancer was significantly higher than that in matched paracancerous tissues.

Embodiment 3

[0106] Example 3, ACAT1 inhibitors can inhibit the growth of liver cancer cells

[0107] In this example, the inventors studied the role of ACAT1 inhibitors in inhibiting the growth of liver cancer cells.

[0108] The results showed that the ACAT1 specific inhibitor K604 and the non-specific inhibitor Avasimibe could significantly inhibit the proliferation of liver cancer cells (HepG2, MHCC97H and Huh7) ( image 3 ,4). It shows that inhibiting ACAT1 can significantly inhibit the proliferation of liver cancer cell lines, suggesting that ACAT1 may be used as a target for liver cancer treatment.

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Abstract

The invention discloses new application of a substance for inhibiting genetic expression and / or protein activity of acyl coenzyme A / cholesterol acyltransferase-1. According to the application, the inhibitor can be used for preparing drugs for preventing and / or treating cancer; the inhibitor can be used for preparing drugs for preventing and / treating cancer spreading and metastasis; the inhibitor can be used for preparing drugs for promoting apoptosis of cancer cells; the inhibitor can be used for preparing drugs for inhibiting cancer cells from being transformed into cancer; the inhibitor canbe used for preparing drugs for inhibiting in vitro proliferation growth of the cancer cells. Through experiments, the inventor proves that the acyl coenzyme A / cholesterol acyltransferase-1 (ACAT1 / SOAT1) is obviously highly expressed in liver cancer tissue, and the high enrichment value of the acyl coenzyme A / cholesterol acyltransferase-1 shows that prognosis of a liver cancer patient is poor. TheACAT1 / SOAT1 inhibitor can effectively inhibit growth of human liver cancer cells and other cancer cells in the cellular level, and the inhibitor can used as a candidate drug target of cancers, especially the liver cancer.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a new drug application of an acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1 / SOAT1) inhibitor. Background technique [0002] The liver is the center of cholesterol metabolism in the body and plays a vital role in maintaining the balance of cholesterol metabolism in the body. The liver can produce large amounts of cholesterol through de novo synthesis. Blood cholesterol levels are significantly positively correlated with the incidence of liver cancer. The level of intracellular cholesterol is very important to the life activities such as cell growth, proliferation and differentiation. Clinical studies have shown that serum cholesterol levels in patients with liver cancer are significantly reduced. However, the cholesterol level in liver cancer tissue was significantly higher than that in paracancerous tissue. Cholesterol in the body can be divided into free choleste...

Claims

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Application Information

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IPC IPC(8): A61K31/496A61P35/00A61P35/02
CPCA61K31/496
Inventor 姜颖孙爱华贺福初李朝英周金安魏汉东王守乾
Owner BEIJING PROTEOME RES CENT
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