The effects of DNA methylation and histone deacetylase inhibitors on human papillomavirus early gene expression in cervical cancer, an in vitro and clinical study.

摘要: The methylation status at the human papilloma virus (HPV) genome found in pre-invasive and invasive cervical lesions suggests that neoplastic transformation can be suppressed by gene hypermethylation, whereas hypomethylation accompanies or causes cancer progression; hence, epigenetic therapy aimed reactivating cellular suppressor-gene expression has potential to act as a tumor promoter enhancing HPV oncoprotein HPV-related malignancies. objective of this study was determine influence hydralazine valproate on oncogene cell lines primary tumors patients undergoing treatment with valproate. Overall, either alone combined exerted growth inhibitory effect lines. A line-specific up-regulating observed E6/E7 expression, which general correlated DNA histone acetylation long control region (LCR). Nonetheless, unchanged decreased majority treated hydralazine, valproate, both. In some lines, these drugs led increased transcription p53, its stabilization due lysines 273 282, allowed higher bax-protein transactivating effect. results demonstrate safely administered malignancies such because they do not increase viral expression. Most importantly, antitumor may least partially depend an p53 valproate-induced hyperacetylation protein, protecting it from degradation E6.