title: Role of mTOR inhibitor in cholangiocarcinoma cell progression.
abstract: Cholangiocarcinoma (CCA) is a lethal malignancy of the biliary epithelium. CCA is resistant to currently available chemotherapy; therefore, new drugs as well as new molecular targets must be identified for the development of an effective treatment for CCA. The present study showed that RAD001 (everolimus), a derivative of rapamycin and an orally bioavailable mammalian target of rapamycin (mTOR) inhibitor, exhibits cytotoxic and antimetastatic effects in a CCA cell line, RMCCA-1. Treatment with low concentrations of RAD001 resulted in a significant reduction ofin vitroinvasion and migration of RMCCA-1, concomitant with a reduction of filopodia and alteration of the actin cytoskeleton. Although, matrix metalloproteinase-9 and -14 activities were unaltered. However, at high concentrations, RAD001 exhibited cytotoxic effects, reducing cell proliferation and inducing apoptotic cell death. Overall, RAD001 exhibits multiple effects mediated by the inhibition of the mTOR, which may serve as a promising agent for the treatment of CCA.
authors: Department of Biochemistry, Faculty of Science, Mahidol University, Rajathevi, Bangkok 10400, Thailand.
authors: Penpak
authors: P
authors: Moolthiya
authors: Department of Biochemistry, Faculty of Science, Mahidol University, Rajathevi, Bangkok 10400, Thailand.
authors: Rutaiwan
authors: R
authors: Tohtong
authors: Department of Molecular Medicine, Faculty of Science, Mahidol University, Rajathevi, Bangkok 10400, Thailand.
authors: Siriporn
authors: S
authors: Keeratichamroen
authors: Department of Surgery, Rajavithi Hospital, Rajathevi, Bangkok 10400, Thailand.
authors: Kawin
authors: K
authors: Leelawat
keywords: RAD001; cholangiocarcinoma; mTOR inhibitor