TAT­fused IP3R­derived peptide enhances cisplatin sensitivity of ovarian cancer cells by increasing ER Ca2+ release.

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 B­cell lymphoma 2 (Bcl­2) BH4 domain has been reported to mediate the prosurvival activity of Bcl­2 in cancer; however, the involvement of the BH4 domain of Bcl­2 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 TAT­fused inositol 1,4,5­trisphosphate receptor­derived peptide (TAT­IDPS), which targets the BH4 domain of Bcl­2, increased cisplatin­induced Ca2+ flux from the endoplasmic reticulum (ER) into the cytosol and mitochondria. In addition, TAT­IDPS increased cisplatin­induced expression of mitochondrial apoptosis­associated proteins and ER stress­associated proteins. These results indicated that TAT­IDPS may enhance the cytotoxicity of cisplatin toward ovarian carcinoma cells by increasing ER Ca2+ release.