Research Of Resveratrol Suppresses The Growth And Invasive Abilities Of Ishikawa Endometrial Cancer Cells Potentially By Regulating MTA1/HDAC1Complex Expression

ObjectiveThis study aims to investigate the function of resveratrol to suppress ERα(+) Ishikawa endometrial cancer cell growth and invasive abilities in vitro, explore the regulation of ERa, HDAC1and MTA1expression by resveratrol, so that we can approach the possible mechanisms involved in the anti-tumor ability of resveratrol. MethodsIshikawa endometrial cancer cells are cultured in vitro and treated with different concentrations of resveratrol (0,25,50,100μM) in different time (0,12,24,48,72h). ERα and MTA1RNA expression is detected by Realtime-PCR. ERa, MTA1and HDAC1protein expression is detected by Western blot analysis. The cells proliferation is detected by MTT assay and the ability of invasion is detected by transwell assay. Results1. Resveratrol significantly inhibits Ishikawa endometrial cancer cells viability and proliferation ability in a dose-dependent manner when treat in24,48and72h while not in12h. Resveratrol significantly inhibits Ishikawa endometrial cancer cells invasive ability in a dose-dependent manner when treat in12,24,48and72h.2. The expression of MTA1mRNA is reduced significantly by resveratrol (p<0.05). The expression of ERa mRNA is increased by resveratrol in a dose-dependent manner. When treated with100μM in12h,25,50and100μM in24h as well as50,100μM in48h and72h, the differences are significant (p<0.01).3. The expression of MTA1and HDAC1protein are reduced significantly by resveratrol in a dose-dependent manner. When treated with50,100μM in12h and48h,25,50and100μM in24h as well as25,50μM in72h, the difference of MTA1expression is significant (p<0.05). When treated with50,100μM in12h,48h and72h as well as25,50and100μM in24h, the difference of HDAC1expression is significant (p<0.05). The expression of ERa protein had no significant change when the cells are treated with resveratrol in12h. But when treated with25,50and100μM in24h as well as25,50μM in48h, the expression of ERa protein is increased. Except25μM in48h, the differences are significant (p<0.05). Unexpectedly, when treated with100μM in48h, the expression of ERa protein is induced.What’s more, after25,50and100μM resveratrol treat cells in72h, the expression of ERa protein is significantly induced in a dose-dependent manner (p<0.05).4、After resveratrol treatment, the expression of MTA1mRNA (Spearman correlation coefficient=0.616, p=0.000), protein (Spearman correlation coefficient=0.514, p=0.000) and HDAC1protein (Spearman correlation coefficients.605, p=0.000) show a positive linear correlation with proliferation ability of Ishikawa cells. At the same time, the expression of MTA1mRNA (r=0.669, p=0.000), protein (r=0.315, p=0.029) and HDAC1protein (r=0.289, p=0.047) also show a positive linear correlation with invasive ability of Ishikawa cells. ConclusionThis study confirms that resveratrol inhibits Ishikawa endometrial cancer cells proliferation and invasive ability in a dose-dependent manner, the mechanism is possiblely associated with regulating the expression of MTA1/HDAC1complex. The regulation of ERa expression is independent on the expression of MTA1/HDAC1complex, it might be involved in resveratrol’s estrogen agonist/antagonist effects, and is influenced by effect concentration and time. The inhibitory effects of resveratrol are independent on ERa expression, while MTA1/HDAC1complex is likely a target of resveratrol. These conclusions provid theory basis for resveratrol’s function as an endometrial cancer suppressor, resveratrol is expected to be a novel effective drug for the treatment of endometrial cancer.