Effects of 7-difluoromethoxyl-5,4'-di-n-octylygenistein on the Actions of Inhibiting Proliferation and Invasion of Cervical Cancer Cells via Inactivating Pim-1

OBJECTIVE To investigate the anti-tumor effects of 7-difluoromethoxyl-5,4'-di-n-octylygenistein (DFOG) on human cervical cancer HeLa cells and its possible molecular mechanism. METHODS HeLa cells were cultured in vitro, and the proliferation inhibitory effects of DFOG was determined using MTT assay. The effect of DFOG on distribution of cell cycle phase was observed using flow cytometry with propidium iodide (PI) staining. The inhibition rate of migration and invasion were valued by Transwell cell assay. Multiple molecular techniques, such as Western blotting, siRNA and cDNA transfection were used to explore the molecular mechanism. RESULTS DFOG presented dramatic anti-tumor activity against HeLa cells in vitro, inhibited the cells proliferation, attenuated the migration and invasion ability in dose-dependent manner, accompanied by cell cycle arrest in G1 phase. DFOG caused proliferation inhibition accompanied with the expression down-regulation of Pim-1 protein and its downstream genes, such as Cyclin D, Cyclin E, Cyclin A, and increased expression p15 and p21. Down-regulation expression of Pim-1 by siRNA followed DFOG treatment resulted in cell proliferation inhibition rate enhanced and migration/invasion ability attenuated. Up-regulation expression of Pim-1 by cDNA transfection attenuated DFOG-induced cell proliferation inhibition and its migration/invasion capability. CONCLUSION DFOG can inhibit proliferation and invasion of human cervical cancer HeLa cells in vitro through inactivated Pim-1 expression accompanied cells in G1 phase.