Co-transduction of Apaf-1 and Caspase-9 Augments Etoposide-induced Apoptosis in U-373MG Glioma Cells |
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Authors: | Nobusada Shinoura Shinya Sakurai Akio Asai Takaaki Kirino Hirofumi Hamada |
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Institution: | Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Cancer Institute, 1-37-1 Kami-lkebukuro, Toshima-ku, Tokyo 170-8455;Departtnent of Neurosurgery, Tokyo University, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655;Department of Neurosurgery, Komagome Metropolitan Hospital, 3-18-22 Hon-Komagome, Bunkyo-ku, Tokyo 113-8677;Department of Biochemistry, Kyoritsu College of Pharmacy, Shibakoen 1-5-30, Minato-ku, Tokyo 105-8512;CREST (Core Research for Evolutional Science and Technology), 2-6-15 Shibakoen, Minato-ku, Tokyo 105-0011;Department of Molecular Medicine, Sapporo Medical University, South 1 West 17, Chuo-ku, Sapporo 060-8556 |
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Abstract: | Several apoptosis-related genes have been reported to be involved in chemotherapy-induced apoptosis in cancers. An assessment of the relationship between expression of those genes and the degree of chemotherapy-induced apoptosis may be useful in improving the efficacy of cancer therapy. We transduced Apaf-1 (apoptotic protease-activating factor-1) and caspase-9 into U-373MG glioma cells using adenovirus (Adv) vectors in the presence of etoposide and evaluated the degree of apoptosis. The degree of apoptosis in etoposide-treated U-373MG cells infected with Adv for Apaf-1 (Adv-APAFl) was higher (27%) than that in cells infected with control Adv (14%), that in cells infected with Adv for caspase-9 (Adv-Casp9) was higher (34%) than that in cells infected with Adv-APAFl, and that in cells infected with both Adv-APAFl and Adv-Casp9 was the highest (41%). Treatment with etoposide increased expression of p53 and decreased expression of Bcl-XL in U-373MG cells which harbored mutant p53. These results indicate that the expression of Apaf-1 and caspase-9 may be important determinants in predicting the sensitivity of cancers to chemotherapy. Adv-mediated co-transduction of Apaf-1 and caspase-9 should render cancer cells highly sensitive to chemotherapy. |
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Keywords: | Apoptosis Etoposide Apaf-1 Caspase-9 Glioma |
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