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Drug for treating hepatocellular carcinoma and application of glucagon-like peptide-1 receptor stimulant and/or dipeptidyl peptidase 4 inhibitor

A technology of glucagon and receptor agonists, applied in the field of application of drugs for the treatment of hepatocellular carcinoma and glucagon-like peptide-1 receptor agonists and/or dipeptidyl peptidase 4 inhibitors, It can solve problems such as undetermined results, and achieve the effect of increasing cancer cell apoptosis, inhibiting cancer cell proliferation, and reducing obesity dependence

Inactive Publication Date: 2017-08-18
SUN YAT SEN UNIV
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Problems solved by technology

Despite the significant association of diabetes and HCC, the consequences of GLP-1R activation in hepatocarcinogenesis remain inconclusive

Method used

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  • Drug for treating hepatocellular carcinoma and application of glucagon-like peptide-1 receptor stimulant and/or dipeptidyl peptidase 4 inhibitor
  • Drug for treating hepatocellular carcinoma and application of glucagon-like peptide-1 receptor stimulant and/or dipeptidyl peptidase 4 inhibitor
  • Drug for treating hepatocellular carcinoma and application of glucagon-like peptide-1 receptor stimulant and/or dipeptidyl peptidase 4 inhibitor

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Experimental program
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Embodiment

[0033] To examine the effect of GLP-1R activation in HCC, we established an HCC model in mice, in which DEN was administered for HCC induction and fed either low-fat and low-carbohydrate (LFLC) or high-fat and high-carbohydrate (HFHC ) diet for NASH development, designed to mimic pathological progression from NASH to HCC. HFHC and DEN treated mice are clinically relevant as the resulting pathological conditions are highly similar to human diabetes and HCC. Here we found that GLP-1R activation by Ex-4 treatment significantly reduced HCC multiplicity in LFLC- and HFHC-fed mice. Of particular interest is that Ex-4 exerts differential effects in a tissue-specific manner, which are mediated by multiple signaling cascades. This information defines a critical role for GLP-1R activation in protecting the liver from developing HCC and provides new mechanistic insights based on this tumor suppressor effect.

[0034] Male C57BL / 6N mice were housed at 22-24°C under a 12-hour light-dark ...

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Abstract

The invention provides a drug for treating hepatocellular carcinoma. The drug comprises a glucagon-like peptide-1 receptor stimulant and / or a dipeptidyl peptidase 4 inhibitor. The invention further provides application of the glucagon-like peptide-1 receptor stimulant and / or dipeptidyl peptidase 4 inhibitor to preparation of a drug for preventing or treating hepatocellular carcinoma, to preparation of a drug for liver function recovery after liver transplantation, and to preparation of a drug for preventing liver cancer relapse after liver transplantation. The glucagon-like peptide-1 receptor stimulant and / or dipeptidyl peptidase 4 inhibitor generates a differential effect in a tissue specificity way, so as to inhibit cancer cell proliferation and promote cancer cell apoptosis, meanwhile, liver cells are protected against apoptosis, so that obesity-dependent liver cancer or non-dependent liver cancer can be treated or weakened.

Description

technical field [0001] The invention relates to a medicine for hepatocellular carcinoma and the application of a glucagon-like peptide-1 receptor agonist and / or a dipeptidyl peptidase 4 inhibitor. Background technique [0002] Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Epidemiological studies have shown that type II diabetes (T2D) is associated with a 3-fold higher risk of HCC. Importantly, multiple T2D-associated pathological conditions, such as hyperglycemia, have been identified as important inducing and prognostic factors for HCC. Nearly 10% of adults in developed countries have diabetes, and the prevalence is increasing every year. Furthermore, 69.5% of T2D patients had non-alcoholic fatty liver disease (NAFLD), which predisposed patients to develop HCC. NAFLD has a broad pathological spectrum from steatosis, steatohepatitis (NASH), fibrosis to cirrhosis. Clinical studies have reported that a...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K38/26A61K31/4985A61P35/00A61P1/16
CPCA61K38/26A61K45/06A61K31/4985
Inventor 徐刚郑诗乐周明艳
Owner SUN YAT SEN UNIV
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