Short hairpin RNA targeting c-FLIP sensitizes human cervical adenocarcinoma Hela cells to chemotherapy and radiotherapy.
c-FLIP inhibits caspase-8 activation and cell apoptosis mediated by death receptors. The present study aims at determining the effects of c-FLIP targeted vector-based short hairpin RNA (shRNA) on cell growth and evaluating its modulation of responsiveness to drugs and radiotherapy in cervical adenocarcinoma Hela cells. cFLIP expression of the cells transfected with shRNA against c-FLIP was significantly down-regulated after 72 h. c-FLIP silencing markedly suppressed cell proliferation and increased cell apoptosis. The activation of caspase-8 and caspase-3 was induced with shRNA targeting cFLIP with the passage of time after transfection. Furthermore, Vector-based shRNA against c-FLIP subsequently increased the sensitivity to cisplatin, iritican and Co60 radiotherapy by about 4- to 6-folds in Hela cells. Our data suggest that vector-based shRNA effectively inhibited c-FLIP expression, enhanced the expression level of caspase-8 and caspase-3 to induce cell apoptosis, probably with the higher efficacy in combination therapies with conventional chemotherapy and radiotherapy in cervical adenocarcinoma.
Luo
Aiyue
A
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
Wang
Wei
W
Sima
Ni
N
Lu
Yunping
Y
Zhou
Jianfeng
J
Xu
Gang
G
Yu
Hongtao
H
Wang
Shixuan
S
Ma
Ding
D
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics*; D053181:Caspase 8 / Q000378:metabolism; D049109:Cell Proliferation; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D012313:RNA / Q000235:genetics*; D011878:Radiotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D012313:RNA; D053181:Caspase 8