EBNA1 may prolong G(2)/M phase and sensitize HER2/neu-overexpressing ovarian cancer cells to both topoisomerase II-targeting and paclitaxel drugs |
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Authors: | Chuang Tzu-Chao Lee Yi-Jen Liu Jah-Yao Lin Yen-Shing Li Jhy-Wei Wang Vinchi Law Sai-Lung Kao Ming-Ching |
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Affiliation: | Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC. |
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Abstract: | 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. |
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Keywords: | HER2/neu EBNA1 Tumorigenicity Ovarian cancer |
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