PMID- 24527093 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211021 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 7 IP - 3 DP - 2014 Mar TI - Role of mTOR inhibitor in cholangiocarcinoma cell progression. PG - 854-860 AB - 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 of in vitro invasion 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. FAU - Moolthiya, Penpak AU - Moolthiya P AD - Department of Biochemistry, Faculty of Science, Mahidol University, Rajathevi, Bangkok 10400, Thailand. FAU - Tohtong, Rutaiwan AU - Tohtong R AD - Department of Biochemistry, Faculty of Science, Mahidol University, Rajathevi, Bangkok 10400, Thailand. FAU - Keeratichamroen, Siriporn AU - Keeratichamroen S AD - Department of Molecular Medicine, Faculty of Science, Mahidol University, Rajathevi, Bangkok 10400, Thailand. FAU - Leelawat, Kawin AU - Leelawat K AD - Department of Surgery, Rajavithi Hospital, Rajathevi, Bangkok 10400, Thailand. LA - eng PT - Journal Article DEP - 20140115 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC3919862 OTO - NOTNLM OT - RAD001 OT - cholangiocarcinoma OT - mTOR inhibitor EDAT- 2014/02/15 06:00 MHDA- 2014/02/15 06:01 PMCR- 2014/01/15 CRDT- 2014/02/15 06:00 PHST- 2013/05/31 00:00 [received] PHST- 2013/11/29 00:00 [accepted] PHST- 2014/02/15 06:00 [entrez] PHST- 2014/02/15 06:00 [pubmed] PHST- 2014/02/15 06:01 [medline] PHST- 2014/01/15 00:00 [pmc-release] AID - ol-07-03-0854 [pii] AID - 10.3892/ol.2014.1799 [doi] PST - ppublish SO - Oncol Lett. 2014 Mar;7(3):854-860. doi: 10.3892/ol.2014.1799. Epub 2014 Jan 15.