Knockdown of eIF4E suppresses cell proliferation, invasion and enhances cisplatin cytotoxicity in human ovarian cancer cells.
Eukaryotic initiation factor 4E (eIF4E) plays an important role in cap-dependent translation. The overexpression of eIF4E gene has been found in a variety of human malignancies. In this study, we attempted to identify the potential effects of eIF4E and explore the possibility of eIF4E as a therapeutic target for the treatment of human ovarian cancer. First the activation of eIF4E protein was detected with m7-GTP cap binding assays in ovarian cancer and control cells. Next, the eIF4E-shRNA expression plasmids were used to specifically inhibit eIF4E activity in ovarian cancer cells line A2780 and C200. The effects of knockdown eIF4E gene on cell proliferation, migration and invasion were investigated in vitro. Moreover, the changes of cell cycle and apoptosis of ovarian cancer cells were detected by flow cytometry. Finally, we investigated the effect of knockdown of eIF4E on the chemosensitivity of ovarian cancer cells to cisplatin in vitro. Our results show there is elevated activation of eIF4E in ovarian cancer cells compared with normal human ovarian epithelial cell line. The results of BrdU incorporation and FCM assay indicate that knockdown of eIF4E efficiently suppressed cell growth and induce cell cycle arrest in G1 phase and subsequent apoptosis in ovarian cancer cells. From Transwell assay analysis, knockdown eIF4E significantly decrease cellular migration and invasion of ovarian cancer cells. We also confirmed that knockdown eIF4E could synergistically enhance the cytotoxicity effects of cisplatin to cancer cells and sensitized cisplatin-resistant C200 cells in vitro. This study demonstrates that the activation of eIF4E gene is an essential component of the malignant phenotype in ovarian cancer, and aberration of eIF4E expression is associated with proliferation, migration, invasion and chemosensitivity to cisplatin in ovarian cancer cells. Knockdown eIF4E gene can be used as a potential therapeutic target for the treatment of human ovarian cancer.
Department of Cardiology, Zhongnan Hospital of Wuhan University, Hubei 430071, P.R. China.
Jing
J
Wan
Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Hubei 430071, P.R. China.
Fang
F
Shi
Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Hubei 430071, P.R. China.
Zhanzhan
Z
Xu
Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Hubei 430071, P.R. China.
Min
M
Zhao
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering; D014162:Transfection
D000970:Antineoplastic Agents; D039561:Eukaryotic Initiation Factor-4E; D034741:RNA, Small Interfering; D002945:Cisplatin