논문검색
Author Su Mi Bae, M.S.1, Yong Wook Kim, M.D.2, Joo Hee Yoon, M.D.2, Jin Young Yoo, M.D.3, Young-Seok Seo, M.D.4, Sang Lyun Nam, M.D.4, Joon Mo Lee, M.D.2, Sung Eun Namkoong, M.D.2 and Chong Kook Kim, Ph.D.5, Yong-Wan Kim, Ph.D.1 and Woong Shick Ahn, M.D.2
Place of duty 1Catholic Research Institutes of Medical Science, Departments of 2Obstetrics and Gynecology and 3Pathology, College of Medicine, The Catholic University of Korea, Seoul; 4Department of Obstetrics and Gynecology, Chungnam National University Hospital, Daejeon; 5College of Pharmacy, Seoul National University, Seoul, Korea
Title Cell-Specific Growth Inhibition of Human Cervical Cancer Cell by Recombinant Adenovirus p53 in vitro and in vivo
Publicationinfo Cancer Research and Treatment 2003 Jun; 035(03): 181-190.
Key_word Cervix neoplasm, Gene therapy, p53 gene
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Abstract Purpose: Despite the significance of the p53 adenoviral vector in cancer gene therapy, an advanced strategy for the development of preferential tumor cell-specific delivery and the long-term persistent gene expression control of p53 are required. In this study, the time-course expression patterns of p53 and E6, on cervical cancer cells, were investigated to obtain a molecular level understanding of the cell-dependent tumor growth suppression effects of a recombinant adenovirus expressing p53, both in vitro and in vivo. Materials and Methods: The expressions of p53 and E6 in CaSki, SiHa, HeLa, HeLaS3, C33A and HT3 cervical cancer cell lines were examined. After infection with AdCMVp53, the cell growth inhibition was studied via cell count, MTT and Neutral red assays. After transfecting the AdCMVp53 and AdCMVLacZ into the cancer cells-xenografted nude mice, the anti-tumor effects were investigated for one month. Results: The p53 protein levels were more notably expressed in the CaSki and HeLa than in the SiHa and HeLaS3. On day 6, the p53 was only detected in the HeLaS3. In contrast, the p53 expression was highly maintained in the C33A and HT3. The E6 mRNA levels gradually decreased in only the CaSki and HeLa. The growth suppression effects also showed cell-dependent patterns, which were consistent with the reciprocal expression patterns of p53 and E6. After transfection of the AdCMVp53, into the CaSki- and SiHa-xenografted nude mice, the tumor size was remarkably decreased in the SiHa cells as compared to that in the AdCMVLacZ transfected mice, indicating cell-specific growth inhibition patterns. Conclusion: The adenovirus-mediated p53 gene transfection was very effective both in vitro and in vivo. Also, the anti-tumor effects were accomplished via the differential role of p53-specific apoptotic cell death, which was dependent on the cervical cancer cell line. (Cancer Research and Treatment 2003;35:181 190)