Pitavastatin and metformin synergistically activate apoptosis and autophagy in pancreatic cancer cells

doi:10.1002/tox.23146

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23639

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23639

Title:	Pitavastatin and metformin synergistically activate apoptosis and autophagy in pancreatic cancer cells
Authors:	Chen, YH;Huang, YC;Yang, SF;Yen, HH;Tsai, HD;Hsieh, MC;Hsiao, YH
Keywords:	anticancer effects;combination index;metformin;pancreatic cancer;pitavastatin
Date:	2021
Issue Date:	2022-08-05T09:40:31Z (UTC)
Publisher:	WILEY
ISSN:	1520-4081
Abstract:	Pancreatic cancer is the seventh leading cause of cancer-related deaths globally. Metformin is the standard first-line of treatment for hyperglycemia in Type 2 diabetes, whereas pitavastatin is a cholesterol-lowering drug used to prevent cardiovascular diseases. Both these agents evidently exert anticancer effects on pancreatic cancer; however, it remains unclear whether cotreatment using them has additive or synergistic anticancer effects on pancreatic cancer. Thus, we herein used the ASPC-1 and PANC-1 cells and treated them with metformin and/or pitavastatin. We performed the cell viability assay, transwell migration assay, and cell cycle analysis using flow cytometry. Western blotting was used to determine protein levels. We found that cotreatment with metformin (30 mM) and pitavastatin (10 mu M) significantly reduced cell viability; caused G0/G1 cell cycle arrest; upregulated the expression levels of Bax, PCNA, cleaved PARP-1, cleaved caspase-3, LC3 II, and p27 (Kip1)/p21(Cip1); and inhibited cell migration. The combination index value for cell viability indicated a synergistic interaction between metformin and pitavastatin. Moreover, cotreating the cells with metformin (30 mM) and pitavastatin (10 mu M) could preserve mitochondrial function, activate AMPK, and inhibit PI3K/mTOR than treatment with metformin or pitavastatin alone. These findings clearly indicated that metformin plus pitavastatin had a synergistic anticancer effect on pancreatic cancer cells, potentially caused due to the activation of AMPK and inhibition of PI3K/mTOR signaling. Altogether, our results provide that use of metformin plus pitavastatin maybe serve as a chemotherapeutic agent for human pancreatic cancer in future.
URI:	http://dx.doi.org/10.1002/tox.23146 https://www.webofscience.com/wos/woscc/full-record/WOS:000642247300001 https://ir.csmu.edu.tw:8080/handle/310902500/23639
Relation:	ENVIRONMENTAL TOXICOLOGY ,2021,v36,issue 8, P1491-1503
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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