Bcl-2 overexpression reduces cisplatin cytotoxicity by decreasing ER-mitochondrial Ca2+ signaling in SKOV3 cells

Xu,Lu; Xie,Qi; Qi,Ling; Wang,Chunyan; Xu,Na; Liu,Weimin; Yu,Yang; Li,Songyan; Xu,Ye

doi:10.3892/or.2017.6164

Bcl-2 overexpression reduces cisplatin cytotoxicity by decreasing ER-mitochondrial Ca2+ signaling in SKOV3 cells

Authors:
- Lu Xu
- Qi Xie
- Ling Qi
- Chunyan Wang
- Na Xu
- Weimin Liu
- Yang Yu
- Songyan Li
- Ye Xu
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Affiliations: Key Laboratory of Colleges and Universities of Jilin, College of Basic Medicine, Jilin Medical University, Jilin, Jilin 132013, P.R. China, Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Intervention, Jilin Municipal People's Hospital, Jilin, Jilin 132000, P.R. China
Published online on: December 19, 2017 https://doi.org/10.3892/or.2017.6164
Pages: 985-992
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recent studies have revealed that a small amount of cisplatin can penetrate into the nucleus and induce intranuclear DNA damage. Specifically, most cisplatin accumulates in and stresses different organelles, including mitochondria, endoplasmic reticulum (ER) and the cytosol, where apoptosis signaling is activated and magnified. Bcl-2, which is mainly localized to ER and mitochondria, is identified as a key regulator of survival and apoptosis. Bcl-2 is reported to block cisplatin-induced apoptosis via regulating Ca2+ signaling in a variety of cancer cell lines. However, its target molecule and the mechanism responsible for its inhibitory effect in ovarian cancer are undefined. The present study revealed that Bcl-2 overexpression reduced cisplatin-induced growth inhibition and apoptosis in SKOV3 human ovarian cancer cells. Furthermore, Bcl-2 inhibited cisplatin-induced Ca2+ release from the ER to the cytoplasm and mitochondria, which reduced cisplatin-induced ER stress-mediated apoptosis through the mitochondrial apoptotic pathway. The overexpression of Bcl-2 inhibited the cisplatin-induced increase in the number of ER-mitochondrial contact sites in SKOV3 human ovarian cancer cells. In addition, the present study provided evidence that Bcl-2 reduced the anticancer activity of cisplatin towards ovarian cancer cells in vivo. These results revealed that Bcl-2 attenuates cisplatin cytotoxicity via downregulating ER-mitochondrial Ca2+ signaling transduction. Thus, Bcl-2 which may be a potential therapeutic target for ovarian cancer.

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