Synergistic Inhibitory Effect Of 1, 25-dihydroxy Vitamin D₃ And All-trans Retinoic Acid On Growth Of Human Ovarian Cancer Cell Lines Ho8910

Objective This study was to investigate the effects of different concentrations of 1,25-dihydroxy vitamin D3[1,25(OH)2D3],all-trans retinoic acid(ATRA)used alone or in combination on cell growth,cell cycle and apoptosis of human ovarian cancer cell lines HO8910 and then explore the molecular mechanism.Methods HO8910 human ovarian canc-er cell lines were cultured in vitro and treated with different concentrations of 1,25(OH)2D3, ATRA or the combination of both chemicals,cell proliferation was evaluated by MTT assay. Cell cycle and apoptosis were analyzed by flow cytometry(FCM).The expression of vitamin D receptor(VDR)and retinoic acid receptor a(RARa)mRNA were detected by reverse tran-scription-polymerase chain reaction(RT-PCR).Results(1)MTT assay results showed that treated with different concentrations of 1,25(OH)2D3,ATRA or in combination could in-hibit the growth of HO8910 cells and elevated the inhibiting rates as compared with the control group(P<0.05).(2)FCM analysis indicated that different concentrations of 1,25(OH)2D3 and ATRA used alone or in combination could change the cell cycle and induced more strongly G1 Phase arrest of HO8910 cells(P<0.05);all of them could induce apoptosis(P<0.05). (3)The RT-PCR results showed that different concentrations of 1,25(OH)2D3 and ATRA used alone or in combination could up-regulate the mRNA of VDR and RARα(P<0.05). All of the effects were more obvious in the combination group than the groups alone.Conclu-sions Different concentrations of 1,25(OH)2D3 and ATRA could inhibit cell growth,in-duce G1 phase arrest of HO8910 cells and apoptosis. They could up-regulate the mRNA of VDR or RARa and then inhibit proliferation of HO8910 cells in a time-and-dose-depend-ent manner. Furthermore,the combination of 1,25(OH)2D3 and ATRA could exert synergisti-cally inhibitory effect on the growth of HO8910 cells.