Combinations of mTORC1 inhibitor RAD001 with gemcitabine and paclitaxel for treating non-Hodgkin lymphoma
Journal
Cancer Letters
Journal Volume
298
Journal Issue
2
Pages
195-203
Date Issued
2010
Author(s)
Chiang C.-T.
Yeh P.-Y.
Gao M.
Chen C.-W.
Yeh L.-C.
Feng W.-C.
Abstract
Single-agent mammalian target of rapamycin complex 1 (mTORC1) inhibitors have recently been reported as effective salvage treatment in non-Hodgkin lymphoma (NHL). The combined effect of mTORC1 inhibitor, RAD001, with chemotherapeutic agents used for relapsed or refractory NHL was examined. Synergistic interactions were observed for RAD001 plus gemcitabine or paclitaxel in six NHL cell lines; enhanced gemcitabine- and paclitaxel-induced caspase-dependent apoptosis associated with down-regulation of mTOR signaling was detected. Synergistic interactions were also observed with RAD001 plus gemcitabine and paclitaxel. In conclusion, synergistic cytotoxicity was observed with RAD001 plus gemcitabine and paclitaxel in NHL cells. Combination therapy with these three drugs should be examined in patients with refractory or relapsed NHL. ? 2010 Elsevier Ireland Ltd.
SDGs
Other Subjects
benzyloxycarbonylvalylalanylaspartyl fluoromethyl ketone; caspase; everolimus; gemcitabine; mammalian target of rapamycin; navelbine; paclitaxel; protein mcl 1; apoptosis; article; cancer cell culture; cancer combination chemotherapy; cell survival; cell viability; controlled study; cytotoxicity; down regulation; drug antagonism; drug potentiation; drug sensitization; enzyme activation; fluorescence activated cell sorting; human; human cell; IC 50; leukemia cell line; nonhodgkin lymphoma; priority journal; protein expression; signal transduction; Western blotting; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Blotting, Western; Caspases; Cell Line, Tumor; Cell Proliferation; Deoxycytidine; Dose-Response Relationship, Drug; Drug Synergism; Enzyme Activation; Humans; Immunosuppressive Agents; Jurkat Cells; Lymphoma, Non-Hodgkin; Paclitaxel; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Mammalia
Type
journal article