细胞内 Ca2+ 增加通过调节人卵巢癌细胞中 iNOS 的表达来降低顺铂耐药性。
Increased intracellular Ca decreases cisplatin resistance by regulating iNOS expression in human ovarian cancer cells.
机构信息
Key Laboratory of Colleges and Universities of Jilin Province, Basic College of Medicine, Jilin Medical University, Jilin, Jilin, China.
Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin, China.
出版信息
Biomed Pharmacother. 2017 Feb;86:8-15. doi: 10.1016/j.biopha.2016.11.135. Epub 2016 Dec 6.
Previous studies have reported that intracellular Ca signals and inducible nitric oxide synthase (iNOS) are involved in cell apoptosis. However, the role of iNOS in cisplatin resistance in ovarian cancer remains unclear. Here, we demonstrate that SKOV3/DDP ovarian cancer cells were more resistant to cisplatin than were SKOV3 ovarian cancer cells. The expression of intracellular Ca and iNOS was more strongly induced by cisplatin in SKOV3 cells than in SKOV3/DDP cells. TAT-conjugated IP3R-derived peptide (TAT-IDP) increased cisplatin-induced iNOS expression and apoptosis in SKOV3/DDP cells. 2-Aminoethoxydiphenyl borate (2-APB) decreased cisplatin-induced iNOS expression and apoptosis in SKOV3 cells. Thus, iNOS induction may be a valuable strategy for improving the anti-tumor efficacy of cisplatin in ovarian cancer.
先前的研究报告指出，细胞内 Ca 信号和诱导型一氧化氮合酶（iNOS）参与细胞凋亡。然而，iNOS 在卵巢癌顺铂耐药中的作用尚不清楚。在这里，我们证明 SKOV3/DDP 卵巢癌细胞对顺铂的耐药性强于 SKOV3 卵巢癌细胞。顺铂在 SKOV3 细胞中诱导的细胞内 Ca 和 iNOS 的表达比在 SKOV3/DDP 细胞中更强。TAT 缀合的 IP3R 衍生肽（TAT-IDP）增加了 SKOV3/DDP 细胞中顺铂诱导的 iNOS 表达和细胞凋亡。2-氨基乙氧基二苯硼酸盐（2-APB）降低了 SKOV3 细胞中顺铂诱导的 iNOS 表达和细胞凋亡。因此，诱导 iNOS 可能是提高卵巢癌中顺铂抗肿瘤疗效的一种有价值的策略。
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