Abstract
Abstract [Objective] The objective of this study was to examine whether estrogen receptor alpha (ERα) is associated with the sensitivity to cisplatin in ovarian cancer cells. [Methods] Using two human ovarian cancer cell lines (Caov-3, Ovcar-3) which express ERα, we investigated the effect of cisplatin on ERα activation. We evaluated the association between ERα activation and Erk cascade in the cells treated with cisplatin. We next examined the antitumor effects of estradiol (E2) with cisplatin by using MTS [3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and Western blot assay. Then, ERα expression was down-regulated in Caov-3 and Ovcar-3 by using lentiviral shRNA against ERα, and we generated batch clonal lines. The nontarget shRNA (NTS) served as control. Finally, we determined the effect of ERα down-regulation on the sensitivity to cisplatin. [Results] Cisplatin induced the phosphorylation of ERα at serine 118 via Erk cascade. Pretreatment with E2 antagonized cisplatin-induced cytotoxicity, and decreased the expression of cleaved PARP induced by cisplatin. Pretreatment of E2 followed by cisplatin increased the expression of Bcl-2, which is anti-apoptotic protein. The shRNA- mediated down-regulation of ERα increased the sensitivity to cisplatin compared with NTS. [Conclusions] These results indicate that E2 promotes resistance to cisplatin via ERα, and down-regulation of ERα may increase efficacy of cisplatin in ovarian cancer. Citation Format: Sohei Matsumura, Tsuyoshi Ohta, Toshifumi Takahashi, Kazuhiro Takahashi, Satoru Nagase. The association between estrogen receptor alpha and platinum sensitivity in ovarian cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5052. doi:10.1158/1538-7445.AM2015-5052
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