Valproic acid exhibits different cell growth arrest effect in three HPV-positive/negative cervical cancer cells and possibly via inducing Notch1 cleavage and E6 downregulation.

摘要: We investigated the effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, and mechanism VPA-induced growth inhibition on three cervical cancer cell lines with different molecular genetic background. found that VPA induced proliferation suppression, apoptosis cycle arrest in all tested lines, an increase Notch1 active form ICN1 as tumor suppressor its target gene HES1. Noteworthy, blocking Notch signaling DAPT resulted ICN1-overexpressing CaSki HT-3 cells. Thus, endogenous may be necessary for survival lines. Furthermore, G1 phase was HeLa cells by while G2 cells, suggesting this arrest. also suppressed oncogene E6 Notch-independent manner, significant E6-overexpressing HPV positive Cell morphological change observed after treatment upregulation EMT transcription factor Snail1. inhibitor partly reversed Snail1 This discovery supports induce at least via activation.