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 ... Kook Kim, Ph.D.5, Yong-Wan Kim, Ph.D.1 and Woong Shick Ahn, M.D.2 ...... Ahn WS, Han YJ, Bae SM, Kim TH, Rho MS, Lee JM,.
Cell-Specific Growth Inhibition of Human Cervical Cancer Cell by Recom binant Adenovirus p53 in vitro and in vivo 1
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Su M i B ae, M.S. , Yong W ook K im , M.D. , Joo Hee Yoon, M.D. , Jin Young Yoo, M.D. , Young-Seok 4 4 2 2 S eo, M.D. , S ang Lyun N am , M.D. , Joon M o Lee, M.D. , S ung E un N am koong, M.D. and C hong 5 1 2 K ook K im , Ph.D. , Y ong-W an K im , Ph.D. and W oong S hick A hn, M.D. 1
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Catholic Research Institutes of Medical Science, Departments of Obstetrics and Gynecology and Pathology, College of 4 Medicine, The Catholic University of Korea, Seoul; Department of Obstetrics and Gynecology, Chungnam National 5 University Hospital, Daejeon; College of Pharmacy, Seoul National University, Seoul, Korea Purpose: Despite the significance of the p53 adenoviral vector in cancer gene therapy, an advanced strategy for the developm ent 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 tum or 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 can cer cell lines were examined. After infection with AdCMV p53, the cell growth inhibition was studied via cell count, MTT and Neutral red assays. After transfecting the AdCMV p53 and AdCM VLacZ into the cancer cells-xenografted nude m ice, the anti-tum or effects were investigated for one m onth. 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 m RNA 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 AdCM Vp53, into the CaSki- and SiHa-xenografted nude m ice, the tum or size was rem arkably decreased in the SiHa cells as com pared to that in the AdCM VLacZ transfected m ice, indicating cell-specific growth inhibition patterns. Conclusion: The adenovirus-m ediated p53 gene transfection was very effective both in vitro and in vivo. Also, the anti-tum or effects were accom plished via the differential role of p53-specific apoptotic cell death, which was dependent on the cervical cancer cell line. (Cancer Research and Treatm ent 2003;35:181-190) Key W ords: Cervix neoplasm , Gene therapy, p53 gene
