Role of mTOR inhibitor in cholangiocarcinoma cell progression

Moolthiya,Penpak; Tohtong,Rutaiwan; Keeratichamroen,Siriporn; Leelawat,Kawin

doi:10.3892/ol.2014.1799

Role of mTOR inhibitor in cholangiocarcinoma cell progression

Authors:
- Penpak Moolthiya
- Rutaiwan Tohtong
- Siriporn Keeratichamroen
- Kawin Leelawat
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Affiliations: Department of Biochemistry, Faculty of Science, Mahidol University, Rajathevi, Bangkok 10400, Thailand, Department of Molecular Medicine, Faculty of Science, Mahidol University, Rajathevi, Bangkok 10400, Thailand, Department of Surgery, Rajavithi Hospital, Rajathevi, Bangkok 10400, Thailand
Published online on: January 15, 2014 https://doi.org/10.3892/ol.2014.1799
Pages: 854-860

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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 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.

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