Application of dimethyldiguanide in preparation of medicaments for preventing or treating hepatocellular carcinoma

Inactive Publication Date: 2013-10-30
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there is no literature report on the therapeutic effect of metformin in hepatocellular carcinoma, and the results of in vivo and in v

Method used

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  • Application of dimethyldiguanide in preparation of medicaments for preventing or treating hepatocellular carcinoma
  • Application of dimethyldiguanide in preparation of medicaments for preventing or treating hepatocellular carcinoma
  • Application of dimethyldiguanide in preparation of medicaments for preventing or treating hepatocellular carcinoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1. The inhibitory effect of metformin on the growth of human hepatocellular carcinoma cell lines in vitro.

[0026] Hepatocellular carcinoma cell lines SMMC7721, Huh7, HCC-LM3, and HepG2 (purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences) in the logarithmic growth phase were seeded in 96-well plates at a density of 2000-3000 cells / well, and replaced with Complete medium containing metformin at different concentrations (with no metformin group as the control, four concentrations of metformin were 1mM, 2mM, 5mM, and 10mM), respectively, at different time points (48 hours and 96 hours) with Cell Counting Kit-8 (CCK-8 kit, purchased from Dojindo, Japan, to detect cell proliferation, for the detection method, see "Experimental Technology of Medical Immunology" (Soochow University Press, date of publication: February 2011).

[0027] The result is as figure 1 As shown, metformin has obvious inhibitory effect on the proliferation of different cel...

Embodiment 2

[0028] Example 2. The inhibitory effect of metformin on the colony formation ability of liver cancer cell lines.

[0029] Hepatocellular carcinoma cell lines SMMC7721, HCC-LM3, and HepG2 in the logarithmic growth phase were seeded in a 6-well plate at a density of 1000 cells / well, and replaced with metformin (set at two concentrations of 2mM and 5mM) after 24 hours. Complete culture medium, and the empty cell group without any stimulation as the control. After culturing in the cell incubator for 10 days, the formed cell clones were stained with crystal violet and counted, and the ratio of the number of cell clones formed by the metformin treatment group to the control group was calculated. The result is as Figure 4 As shown, the number of cell clones formed by the three types of cells was significantly reduced after metformin treatment, suggesting that metformin can inhibit the malignant transformation ability of liver cancer cells.

Embodiment 3

[0030] Example 3. The inhibitory effect of metformin combined with chemotherapy drugs on the growth of human hepatocellular carcinoma cell lines in vitro.

[0031] Hepatocellular carcinoma cell lines SMMC7721, HCC-LM3, and HepG2 in the logarithmic growth phase were seeded in 96-well plates at a density of 2000-3000 cells / well, and replaced with metformin and cisplatin (purchased from Sigma) after 24 hours. ) complete culture medium, set up a blank control (empty cells without any stimulation), a single metformin (2mM-5mM) control, and a single cisplatin (0.5-2ug / ml) control. After acting for 24 hours, the detection results by CCK-8 method are as follows: Figure 5 , when metformin and cisplatin were used in combination, the survival rate of liver cancer cell lines was significantly lower than that of cisplatin alone, suggesting that the combination of metformin and cisplatin can enhance the inhibitory effect on the growth of liver cancer cell lines.

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Abstract

The invention relates to the technical field of medicaments. Dimethyldiguanide belongs to a biguanides oral hypoglycemic medicament and is widely applied to pharmaceutical therapy of type 2 diabetes. The invention aims at providing a novel application of the dimethyldiguanide and particularly an application of the dimethyldiguanide in preparation of medicaments for preventing or treating the hepatocellular carcinoma. According to the application disclosed by the invention, the restriction effect of the dimethyldiguanide on the hepatocellular carcinoma is found by research from two aspects, namely, cell culture in vitro and animal experiment in vivo. Experiments find that the dimethyldiguanide has the capabilities of restricting proliferation and clone formation of a hepatocellular carcinoma cell line and causing the cell cycle arrest and apoptosis increase of the hepatocellular carcinoma cell line, and also has the capability of enhancing the hepatocellular carcinoma resisting effect of chemotherapeutics when combined with the chemotherapeutics, such as cis-platinum, doxorubicin and the like. The invention provides the novel application of the dimethyldiguanide and also provides a novel concept for prevention and treatment of the hepatocellular carcinoma.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of metformin in the preparation of drugs for preventing or treating hepatocellular carcinoma. Background technique [0002] Primary hepatocellular carcinoma (HCC) is the fifth most common tumor and the third leading cause of cancer-related death in the world. Hepatocellular carcinoma is common in developing countries, especially in East Asia, Southeast Asia, the Pacific Basin, and sub-Saharan Africa. Of the 626,000 reported cases of HCC, approximately 410,000 were in East Asia (346,000 in China and 40,000 in Japan). However, due to the high incidence of invasion and metastasis before treatment, the prognosis of HCC is poor, with a 5-year recurrence rate of 40%-70%. [0003] Metformin is a biguanide oral hypoglycemic drug widely used in the drug treatment of type 2 diabetes. Metformin inhibits gluconeogenesis in the body mainly by activating the AMPK pathway in...

Claims

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Application Information

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IPC IPC(8): A61K31/155A61P1/16A61P35/00
Inventor 王红阳郑龙轶杨文邹大进
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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