The Effect And Mechanism Of Resveratrol On Proliferation Of Breast Cancer Cell Line MCF-7

Objective: Resveratrol, a naturally occurring compound, has anti-cancer effect. Theexact mechanism, however, is unclear. The initiation and progression of cancer areassociated with dysregulated expression of multiple cytokines, which may beregulated by Tristetraprolin(TTP), a mRNA-binding protein. The present study is toinvestigate the expression of TTP in human breast cancer, and observe the role of TTPin the anti-cancer effect of resveratrol in breast cancer cell line MCF-7.Methods:87consecutive patients with suspected breast cancer were admitted to thefirst affiliated hospital of university of south china between May1,2010and May1,2012. The carcinous tissues including ductal carcinoma in situ (n=36) and infitratingductal carcinoma(n=51) were collected. And12pericarcinous tissue were included asthe control group. The mRNA expression of three well-characterized ARE-bindingproteins including TTP、AUF1and HuR were evaluated by Real-time quantitativePCR(RT-PCR). The protein expression of TTP in human breast cancer wasdetermined by Western-blot and immunohistochemical techniques. Human breastcancer MCF-7cells were cultured in DMEM at37℃, and treated with resveratrol (20μM) for48h, the proliferation assay was evaluated by MTT and FCM respectively.MCF-7cells were treated to esveratrol with different concentrations(0,10,20,40μM)for6hours or exposed to20μM esveratrol for different periods of time(0、2、4、8h).The mRNA and protein levels for TTP, COX-2, VEGF and iNOS were evaluated byRT-PCR and Western-blot. After treated with siRNA for TTP in MCF-7cells, theproliferation rate of MCF-7cells and the expression of COX-2and VEGF wereperformed by MTT, RT-PCR and Western-blot. Results: The mRNA of AUF1and HuR were not significantly dysregulated in breastcancer. However, TTP mRNA levels were significantly decreased in different breasttumor types. The protein level of TTP has significantly decreased in breast cancertissues such as ductal carcinoma in situ(DCIS) and invasive ductal carcinoma(IDC).Compared with the comtrol MCF-7cells, the proliferation rates of MCF-7cellstreated with resveratrol was significantly decreased. Resveratrol obviously increasedthe expression of TTP and iNOS at mRNA and protein levels in dose-andtime-dependent manner. In addition, the expression of COX-2and VEGF weresignificantly decreased by resveratrol. After treated with siRNA for TTP, the regulatedeffect of resveratrol on proliferation of MCF-7cells and the expression of COX-2,VEGF and iNOS were significantly impaired.Conclusions: The present study established that TTP expression is suppressed inhuman breast cancer. And upregulation of TTP by resveratrol inhibits the proliferationof the MCF-7cells, which may have related to the decreased expression of COX-2and VEGF and the increased expression of iNOS.