Osmotic Stress Affects Cis-platinum Chemosensitivity Which Is Closely Related To AQP5Expressions In Ovarian Cancer

Purpose. Aquaporins (AQPs) are important mediators of water permeability and are closely associated with tumor cell proliferation, migration, angiogenesis and chemoresistance. Chemosensitivity of tumor cells to cis-platinum (c-DDP) might be affected by osmotic pressure. This study was undertaken to determine whether hyperosmosis regulates ovarian cancer cell sensitivity to c-DDP in vitro and to explore whether this is related to AQP expression.Methods. Ovarian cancer cells were treated with hypertonic medium or c-DDP for determined time, followed by measuring inhibition of cell proliferation using MTT assays. AQPs expressions in response to osmotic pressure or c-DDP were measured by quantitative RT-PCR and Western blot. Cell proliferation in response to hypertonic stress was measured after AQP5was knockdown by siRNA.Results.3AO cell proliferation was inhibited by hyperosmotic stress, while AQP5expressions were increased in dose-and time-dependent manners in hypertonic medium. When AQP5was silenced by siRNA, cells were susceptible to hypertonic stress. Results showed that inhibition of cell proliferation by low dose c-DDP increased significantly with exposure to hyperosmotic stimulus, and this effect was reduced by high dose c-DDP. AQP5expression was induced by low dose c-DDP, but was reduced by high dose c-DDP. However, hyperosmosis enhanced gene AQP5expression at every dose of c-DDP tested, compared with isotonic medium. Thus, the effects of hyperosmosis on cell sensitivity to c-DDP were associated with AQP5expression.Conclusion. These results suggest that cell sensitivity to c-DDP can be regulated by hyperosmosis in ovarian cancer which was associated to AQP5expressions.