TAT‑fused IP3R‑derived peptide enhances cisplatin sensitivity of ovarian cancer cells by increasing ER Ca2+ release

Xie,Qi; Xu,Ye; Gao,Weinan; Zhang,Yong; Su,Jing; Liu,Yanan; Guo,Yuting; Dou,Minghan; Hu,Kebang; Sun,Liankun

doi:10.3892/ijmm.2017.3260

TAT‑fused IP3R‑derived peptide enhances cisplatin sensitivity of ovarian cancer cells by increasing ER Ca2+ release

Authors:
- Qi Xie
- Ye Xu
- Weinan Gao
- Yong Zhang
- Jing Su
- Yanan Liu
- Yuting Guo
- Minghan Dou
- Kebang Hu
- Liankun Sun
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Affiliations: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Histology and Embryology, Basic College of Medicine, Jilin Medical University, Jilin, Jilin 132013, P.R. China, Department of Clinical Medicine, College of Clinical Medicine, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Urology, First Hospital of Jilin University, Changchun, Jilin 130031, P.R. China
Published online on: November 16, 2017 https://doi.org/10.3892/ijmm.2017.3260
Pages: 809-817
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer is the most common gynecological malignancy. At present, cisplatin is used to treat ovarian cancer; however, the development of cisplatin resistance during therapy is a common obstacle to achieving favorable outcomes. Recently, the B‑cell lymphoma 2 (Bcl‑2) BH4 domain has been reported to mediate the prosurvival activity of Bcl‑2 in cancer; however, the involvement of the BH4 domain of Bcl‑2 in the cisplatin resistance of ovarian carcinoma cells is not entirely clear. In this study, we observed the cytoplasmic and mitochondrial levels of Ca2+ by confocal laser microscopy. We also detected cell apoptosis using western blot analysis and flow cytometry. The present study demonstrated that TAT‑fused inositol 1,4,5‑trisphosphate receptor‑derived peptide (TAT‑IDPS), which targets the BH4 domain of Bcl‑2, increased cisplatin‑induced Ca2+ flux from the endoplasmic reticulum (ER) into the cytosol and mitochondria. In addition, TAT‑IDPS increased cisplatin‑induced expression of mitochondrial apoptosis‑associated proteins and ER stress‑associated proteins. These results indicated that TAT‑IDPS may enhance the cytotoxicity of cisplatin toward ovarian carcinoma cells by increasing ER Ca2+ release.

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