Knockdown of eIF4E suppresses cell growth and migration, enhances chemosensitivity and correlates with increase in Bax/Bcl-2 ratio in triple-negative breast cancer cells.
Elevated activity of the eukaryotic translation initiation factor 4E (eIF4E) plays crucial roles in tumorigenesis and disease progression by disproportionately increasing translation of mRNAs coding proteins that play significant roles in all aspects of malignancy, providing that eIF4E as an attractive target for therapeutic intervention. In this study, we showed that inhibition of eIF4E by small interfering RNAs (siRNA) resulted in cell cycle arrest and suppression of colony formation in MDA-MB-231 triple-negative (TN) breast cancer cells. Migration transwell assay revealed that repression of eIF4E effectively inhibited motility of MDA-MB-231 cancer cells. Importantly, we showed that silencing of eIF4E sensitized MDA-MB-231 cells to chemotherapeutic drugs of cisplatin, adriamycin, paclitaxel and docetaxel as assessed by MTT assay. Moreover, Western blot assay showed that eIF4E siRNA increased Bax/Bcl-2 ratio in MDA-MB-231 cells. Taken together, we showed that knockdown of eIF4E suppressed cell growth and migration, enhanced chemosensitivity, suggesting a potential therapeutic target in TN breast carcinoma.
Zhou
Fei-fei
FF
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, and Department of Cancer Center, The First People's Hospital of Foshan, 651 Dongfeng Road East, 510060, Guangzhou, China.
Yan
Min
M
Guo
Gui-fang
GF
Wang
Fang
F
Qiu
Hui-juan
HJ
Zheng
Fei-meng
FM
Zhang
Yan
Y
Liu
Qiang
Q
Zhu
Xiao-feng
XF
Xia
Liang-ping
LP
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; 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; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D039561:Eukaryotic Initiation Factor-4E; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051028:bcl-2-Associated X Protein; C508053:ERBB2 protein, human