Research ArticleOpen Access

Evodiamine Induces Extrinsic Apoptosis Through P38 Mapk Pathway and Inhibits Autophagy in Gallbladder Cancer

Volume 6 - Issue 3

Jun jie Xu¹,Ran Yang¹, Fang jing Yang¹,and Ying bin Liu^2,3*

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- ¹ Shanghai Jiao Tong University School of Medicine, China
- ²Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, China
- ³Institute of Biliary Disease Research, Shanghai Jiao Tong University School of Medicine, China
*Corresponding author: Ying-bin Liu, Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine& Institute of Biliary Disease Research, Shanghai Jiao Tong University School of Medicine, NO.1665 Kongjiang Road, Shanghai, China

Received: June 22, 2018; Published: July 05, 2018

DOI: 10.26717/BJSTR.2018.06.001347

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Abstract

The gallbladder cancer is the most common malignant tumor of the biliary tract and the third most common gastrointestinal malignant tumor in the world for public health with extremely poor prognosis. The primary purpose of this study is to investigate the inhibition effects of evodiamine, a major alkaloid compound extracted from the dry unripened fruit Evodiae fructus, on the carcinoma of the gallbladder cancer, and explored the underlying molecular mechanisms responsible for these effects. Cell viability of NOZ and GBC-SD cells was assessed by CCK-8 and colony forming assays. Cell apoptosis was analyzed by Annexin V-FITC and PI double staining flow cytometry and the apoptosis-related DNA damage was detected by Immunofluorescence microscopy assays. Western blot analysis was used to analyze the expression of crucial proteins involved in apoptosis, autophagy and signaling pathways. In this study, we found evodiamine induced cell viability and colony forming inhibition, apoptosis promotion and autophagy inhibition of NOZ and GBC-SD cells in a dose-dependent manner. The activation of p38 MAPK signaling pathway was significantly associated with evodiamine-treated apoptosis of gallbladder cancer cells, and the depletion of p53 was related with decreasing autophagy. Consequently, we propose that evodiamine may serve as a potential therapeutic agent for gallbladder cancer.

Keywords: Evodiamine; Gallbladder Cancer; Apoptosis; P38 MAPK pathway; Autophagy

Abbreviations: EVO: Evodiamine; C-caspase3 & C-caspase8: Cleaved caspase-3; Cleaved caspase-8; P38 MAPK Pathway: p38 Mitogen Activated Protein Kinase Pathway; LC3 II:Microtubule-Associated Protein 1 light 3 II