The Changes of Cell Cycle Regulatory Proteins Expression by AdCMVp53 in Cervical Cancer Cell Lines / 대한산부인과학회잡지

ABSTRACT

OBJECTIVE: In this study, we investigated the cell growth inhibition, regulation of cell cycle and induction of apoptosis through recombinant p53 adenoviral vector delivery into cervical cancer cell line SiHa, to explore the possibility of p53 gene therapy. METHODS: We infected SiHa with AdCMVp53 at 50 MOI. After 48 hours, the regulation of cell cycle and apoptosis were investigated with FACS. The gene expression profiling associated with cell cycle was also investigated with cell cycle DNA membrane chip. RESULTS: SiHa cells were arrested in the G1 phase by AdCMVp53 and showed cell growth inhibition via apoptosis. The gene expression profiles involved in cell cycle including cyclin-dependent kinase inhibitor 1C (p57, Kip2), RAD9 (S.pombe) homolog, and MAD2 (mitoticarrest deficient, yeast, homolog)-like 2 were up-regulated by more than three-fold, as compared to control group. In contrast, 6 genes such as retinoblastoma-like 2 (p130), and cyclin H were down-regulated by more than three-fold. Several genes known as being differentially up- or down-regulated compared to control were confirmed by RT-PCR and Western blotting assays. CONCLUSION: The adenoviral p53 gene delivery into cervical cancer cell line, suggesting the possibility of p53 gene therapy in cervical neoplasia make the cell growth inhibition and changes of cell cycle-associated gene expression.