EBNA1 may prolong G(2)/M phase and sensitize HER2/neu-overexpressing ovarian cancer cells to both topoisomerase II-targeting and paclitaxel drugs.
We have shown previously that the Epstein-Barr virus nuclear antigen-1 (EBNA1) can act as a transforming suppressor in the HER2/neu-overexpressing ovarian cancer cells. In the present study, by using flow cytometric analysis, we demonstrate that EBNA1 could prolong G(2)/M phase and sensitize to Taxol-induced apoptosis in the EBNA1-expressing ovarian cancer cell stable transfectants. In addition, EBNA1 could also significantly increase topoisomerase IIalpha protein expression, indicating that the up-regulation of topoisomerase IIalpha may be one of the mechanisms by which EBNA1 enhances the sensitivity of ovarian cancer cells to topoisomerase II-targeting anticancer drugs, such as VP-16 and Adriamycin. These data suggest that EBNA1 not only prolongs cell cycle at G(2)/M phase and up-regulates topoisomerase IIalpha expression in HER2/neu-overexpressing ovarian cancer cells, but also increases cellular apoptosis through sensitization of cancer cells to topoisomerase II-directing anticancer drugs.
Chuang
Tzu-Chao
TC
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Lee
Yi-Jen
YJ
Liu
Jah-Yao
JY
Lin
Yen-Shing
YS
Li
Jhy-Wei
JW
Wang
Vinchi
V
Law
Sai-Lung
SL
Kao
Ming-Ching
MC
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004317:Doxorubicin / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D016195:G2 Phase; D015316:Genetic Therapy; D006801:Humans; D007700:Kinetics; D008938:Mitosis; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D017239:Paclitaxel / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D019309:Epstein-Barr Virus Nuclear Antigens; D005047:Etoposide; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D059005:Topoisomerase II Inhibitors; C417029:EBV-encoded nuclear antigen 1