Metformin enhances cisplatin induced inhibition of cholangiocarcinoma cells via AMPK-mTOR pathway

Life Sciences
Jaroon WandeeVeerapol Kukongviriyapan

Abstract

AMP-activated protein kinase (AMPK) functions as a cellular energy sensor regulating various aspects of cellular metabolism. Metformin (Met), an activator of AMPK, has been reported to reduce the cancer risk and enhance antitumor effects in certain cancers. Cholangiocarcinoma (CCA) is an aggressive malignancy which rarely responds to chemotherapeutic agents. We investigated the chemosensitizing effects of Met in CCA cells. KKU-100 and KKU-452 cells were used in the study. Antiproliferation of Met and cisplatin (Cis) was analyzed by sulforhodamine B and colony forming assays. Apoptotic cell death was analyzed by acridine orange and ethidium bromide staining method. Cell cycle analysis was performed by flow cytometric method. Effects on cell migration and invasion were analyzed by wound healing assay and transwell chamber method. Expression of proteins was examined by western blot analysis. Met enhanced the antiproliferation of Cis, and conferred antimigration and anti-invasion in CCA cells, where Cis alone did not have two latter effects. This chemosensitizing effect is related to the activation of AMPK and suppression of Akt, mTOR and p70S6K. Met and Cis increased expression of p53 and p21 and suppressed expression of cyclin D1...Continue Reading

Citations

Sep 8, 2018·Journal of Cellular Physiology·Peiwen LiZhenning Wang
May 10, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Rattanaporn JaideeVeerapol Kukongviriyapan
Jan 27, 2019·International Journal of Molecular Sciences·Chao-En WuChun-Nan Yeh
Nov 17, 2020·Frontiers in Oncology·Chin-Hsiao Tseng
Nov 22, 2020·Canadian Journal of Diabetes·Charupong SaengboonmeeSopit Wongkham
Apr 15, 2021·Cancer Cell International·Nahid AlimoradiReihaneh Fatehi
Jun 5, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Jaroon WandeeVeerapol Kukongviriyapan
Jul 23, 2021·Expert Opinion on Investigational Drugs·Watcharin LoilomeSureerat Padthaisong

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