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- Title
Failure of Elevating Calcium Induces Oxidative Stress Tolerance and Imparts Cisplatin Resistance in Ovarian Cancer Cells.
- Authors
Liwei Ma; Hongjun Wang; Chunyan Wang; Jing Su; Qi Xie; Lu Xu; Yang Yu; Shibing Liu; Songyan Li; Ye Xu; Zhixin Li
- Abstract
Cisplatin is a commonly used chemotherapeutic drug, used for the treatment of malignant ovarian cancer, but acquired resistance limits its application. There is therefore an overwhelming need to understand the mechanism of cisplatin resistance in ovarian cancer, that is, ovarian cancer cells are insensitive to cisplatin treatment. Here, we show that failure of elevating calcium and oxidative stress tolerance play key roles in cisplatin resistance in ovarian cancer cell lines. Cisplatin induces an increase in oxidative stress and alters intracellular Ca2+ concentration, including cytosolic and mitochondrial Ca2+ in cisplatin-sensitive SKOV3 cells, but not in cisplatin-resistant SKOV3/DDP cells. Cisplatin induces mitochondrial damage and triggers the mitochondrial apoptotic pathway in cisplatin-sensitive SKOV3 cells, but rarely in cisplatin-resistant SKOV3/DDP cells. Inhibition of calcium signaling attenuates cisplatininduced oxidative stress and intracellular Ca2+ overload in cisplatin-sensitive SKOV3 cells. Moreover, in vivo xenograft models of nude mouse, cisplatin significantly reduced the growth rates of tumors originating from SKOV3 cells, but not that of SKOV3/DDP cells. Collectively, our data indicate that failure of calcium up-regulation mediates cisplatin resistance by alleviating oxidative stress in ovarian cancer cells. Our results highlight potential therapeutic strategies to improve cisplatin resistance.
- Subjects
OXIDATIVE stress; CISPLATIN; OVARIAN cancer
- Publication
Aging & Disease, 2016, Vol 7, Issue 3, p254
- ISSN
2152-5250
- Publication type
Article
- DOI
10.14336/AD.2016.0118