Inhibitory effect of Epigallocatechin gallate on ovarian cancer cell proliferation associated with aquaporin 5 expression

Abstract

Abnormal expression of aquaporin 5 (AQP5) is associated with ovarian cancer infiltration, metastasis and angiogenesis. AQP 5 expression and apoptosis have been shown to be closely related to nuclear transcription factor NF-κB. In this study, we investigated the inhibition of cell proliferation and the induction of apoptosis by Epigallocatechin gallate (EGCG), a potential anti-cancer drug, in the ovarian cancer cell line SKOV3 as well as the effect of EGCG on AQP5 expression and its possible mechanisms. SKOV3 cells were treated with different concentrations of EGCG and the NF-κB-specific inhibitor pyrrolidine dithiocarbamate (PDTC) for different times. Cell proliferation was determined using the MTT assay, cell apoptosis was evaluated using the DNA ladder assay, the expression of AQP5, NF-κB p65 and IκBα was detected by immunohistochemistry, western blot analysis and RT-PCR, and the correlation of these protein expression was analyzed. With increasing concentrations of EGCG and prolonged treatment times, the growth inhibition rate of SKOV3 cells gradually increased in a dose- and time-dependent manner. The expression of AQP5 and nuclear p65 and IκBα was significantly decreased (P < 0.01). The cytoplasmic expression of IκBα gradually increased (P < 0.05), and the apoptosis of SKOV3 cells was induced as evidenced by typical fragmentation pattern in a DNA ladder assay. With increasing concentrations of PDTC and prolonged treatment times, the protein and mRNA levels of AQP5 in SKOV3 cells decreased (P < 0.01). In addition, the growth inhibition rate of SKOV3 cells significantly increased in a dose- and time-dependent manner. EGCG inhibited the proliferation and induced the apoptosis of ovarian cancer SKOV3 cells. EGCG also down-regulated expression of AQP5, which may inhibit tumor growth and be associated with nuclear transcription factor NF-κB.