Publication: Role of mTOR inhibitor in cholangiocarcinoma cell progression
3
Issued Date
2014-03-01
Resource Type
ISSN
17921082
17921074
17921074
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2-s2.0-84892994601
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Mahidol University
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SCOPUS
Bibliographic Citation
Oncology Letters. Vol.7, No.3 (2014), 854-860
Suggested Citation
Penpak Moolthiya, Rutaiwan Tohtong, Siriporn Keeratichamroen, Kawin Leelawat Role of mTOR inhibitor in cholangiocarcinoma cell progression. Oncology Letters. Vol.7, No.3 (2014), 854-860. doi:10.3892/ol.2014.1799 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/33294
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Title
Role of mTOR inhibitor in cholangiocarcinoma cell progression
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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.