GYNECOLOGIC ONCOLOGY Inhibitory effect of Epigallocatechin gallate on ovarian cancer cell proliferation associated with aquaporin 5 expression Chunxiao Yan • Jianhua Yang • Lan Shen • Xuejun Chen Received: 16 November 2010 / Accepted: 31 May 2011 / Published online: 23 June 2011 Ó Springer-Verlag 2011 Abstract Objective 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-jB. In this study, we investigated the inhibition of cell proliferation and the induction of apoptosis by Epigallo- catechin 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. Methods SKOV3 cells were treated with different con- centrations of EGCG and the NF-jB-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-jB p65 and IjBa was detected by immunohistochemistry, western blot analysis and RT-PCR, and the correlation of these protein expres- sion was analyzed. Results 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 IjBa was significantly decreased (P \ 0.01). The cytoplasmic expression of IjBa 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. Conclusions 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-jB. Keywords EGCG Á Ovarian cancer Á Aquaporin 5 Á Cell proliferation Á NF-jB Introduction Tea is a popular beverage worldwide, ranking only second to water. Tea polyphenols are extracted from green tea, and their main active ingredient is Epigallocatechin gallate (EGCG). EGCG has many biological activities and phar- macological effects, such as anti-tumor, anti-mutagenic, anti-inflammation and free radical scavenging and antiox- idant activities [1]. EGCG has been reported to have anti- cancer biological activity as well; the main mechanism of this activity involves the inhibition of cell proliferation and the induction of apoptosis [2]. EGCG can inhibit the pro- liferation of cells from skin cancer, lung cancer, oral can- cer, gastric cancer, intestinal cancer, colon cancer, hepatocellular carcinoma, pancreatic cancer, rectal cancer, prostate cancer and breast cancer, suggesting that EGCG could be utilized as a potential anti-cancer drug [3–8]. C. Yan Á J. Yang (&) Á X. Chen Department of Gynecology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China e-mail: yjh0121@126.com C. Yan e-mail: chat_coco@163.com L. Shen Department of Obstetrics and Gynecology, Hangzhou Red Cross Hospital, Hangzhou, China 123 Arch Gynecol Obstet (2012) 285:459–467 DOI 10.1007/s00404-011-1942-6