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Applications of regulator of calcineurin 1.4 or analogues thereof in preparing medicines for inhibiting liver cancer

A technology of calcineurin and regulatory protein, applied in the field of biomedicine, can solve problems such as unclear function of liver cancer

Inactive Publication Date: 2018-12-04
SHANGHAI INST OF ONCOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In the art, the functional role of CaN in primary liver cancer is unclear

Method used

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  • Applications of regulator of calcineurin 1.4 or analogues thereof in preparing medicines for inhibiting liver cancer
  • Applications of regulator of calcineurin 1.4 or analogues thereof in preparing medicines for inhibiting liver cancer
  • Applications of regulator of calcineurin 1.4 or analogues thereof in preparing medicines for inhibiting liver cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0188] Example 1. The expression level of RCAN1.4 in tumor tissue was significantly down-regulated

[0189] There are three detectable alternative splice forms of RCAN1 in mammalian tissues (RCAN1.1, RCAN1.2 and RCAN1.4). Through quantitative PCR detection of 108 pairs of liver cancer tissues (Cancerous tissues from human hepatocellular carcinomas, referred to as C) and paired non-cancerous liver tissues (abbreviated as N) collected by Dongfang Hepatobiliary Hospital, it was found that: and RCAN1.2 mRNA expression levels in liver cancer tissues and paired paracancerous liver tissues were extremely low, and there was no statistical difference ( figure 1 , A); The expression level of RCAN1.4mRNA in the non-cancerous liver tissue was very high, while it was significantly down-regulated in the paired liver cancer tissue samples ( figure 1 , A), the minimum down-regulation multiple is about 20 times ( figure 1 , B), wherein the number of cases whose expression was down-regulated ...

Embodiment 2

[0191] Example 2. Increasing the expression of RCAN1.4 can inhibit the proliferation, migration and invasion of liver cancer cells in vitro

[0192] In order to study the effect of RCAN1.4 on the function of liver cancer cells in vitro, the inventors used lentiviral transfection to construct RCAN1.4 overexpression stable cells and their control cells (MHCC97H and HCCLM3) in liver cancer cells, and detected the proliferation of liver cancer cells in vitro , changes in migration and invasion capabilities.

[0193] The results of CCK-8 experiment showed that after overexpression of RCAN1.4, the proliferation ability of liver cancer cells was significantly reduced ( figure 2 , A).

[0194] The results of cell migration experiments showed that after overexpression of RCAN1.4, the migration ability of liver cancer cells was significantly reduced ( figure 2 , B).

[0195] The results of Matrigel cell invasion assay showed that after overexpression of RCAN1.4, the invasion abilit...

Embodiment 3

[0197] Example 3. Overexpression of RCAN1.4 can effectively inhibit the progression of liver cancer

[0198] In order to study the effect of RCAN1.4 on the growth and metastasis of liver cancer cells in vivo, the inventors used lentiviral transfection to construct RCAN1.4 overexpression stable cells and their control cells (MHCC97H and HCCLM3) in liver cancer cells, and established nude mice Liver orthotopic tumorigenesis model.

[0199] In nude mouse liver orthotopic tumorigenesis model, the liver was orthotopically inoculated with hepatocellular carcinoma cells (MHCC97H-RCAN1.4 and HCCLM3-RCAN1.4) and control cells (MHCC97H-Vector and HCCLM3-Vector) overexpressing RCAN1.4, After feeding for a certain period of time, the orthotopic liver tumors of the nude mice were collected, and the volume of the liver tumors in each group was calculated. At the same time, HE staining was performed on the lung tissues of each group to count the number of lung metastases.

[0200] The resul...

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Abstract

The invention relates to applications of a regulator of calcineurin 1.4 (RCAN1.4) or analogues of RCAN1.4 in preparing medicines for inhibiting liver cancer. According to the applications, RCAN1.4 orup-regulators of RCAN1.4 can be used for inhibiting liver cancer; and the functional analogue medicines such as cyclosporin A of RCAN1.4 also can obviously reduce the in-vivo pulmonary metastasis capacity of liver cancer cells.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically, the invention relates to the application of calcineurin regulatory protein 1.4 or its analogs in the preparation of drugs for inhibiting liver cancer. Background technique [0002] Primary liver cancer (Hepatocellular Carcinoma, HCC, hereinafter referred to as liver cancer) is one of the malignant tumors that seriously threaten human health. Globally, its mortality rate ranks second among men and fifth among women. Liver cancer is also one of the four most common tumors in China. More than 50% of the world's primary liver cancers occur in China, and the incidence rate ranks first in the world. Early diagnosis and treatment of liver cancer is difficult, the disease progresses rapidly and the prognosis is poor, and the vast majority of patients with liver cancer die of tumor metastasis and recurrence. According to clinical research data, even with radical surgery, the recurrence r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K38/17A61K31/436A61K38/13A61P35/00C12Q1/02
CPCA61K31/436A61K38/13A61K38/1709A61K38/1761A61K45/00C12N2503/02G01N33/5011G01N33/5067G01N2500/10
Inventor 覃文新金浩杰
Owner SHANGHAI INST OF ONCOLOGY
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