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.
[1]Jilin Univ, Basic Coll Med, Dept Pathophysiol, 126 Xinmin St, Changchun 130021, Jilin, Peoples R China.
[2]Jilin Med Univ, Basic Coll Med, Dept Histol & Embryol, Jilin 132013, Jilin, Peoples R China.
[3]Jilin Univ, Coll Clin Med, Dept Clin Med, Changchun 130021, Jilin, Peoples R China.
[4]Jilin Univ, Hosp 1, Dept Urol, 3302 Jilin St, Changchun 130031, Jilin, Peoples R China.
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