Melatonin synergistically enhances cisplatininduced cell proliferation suppression of Hep2 human laryngeal cancer cells by promoting apoptosis
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Abstract:
Objective:Toinvestigate the effect of melatonin (MT) on humanlaryngeal cancercells and its ability to enhance the sensitivity of humanlaryngeal cancercells tocisplatin (DDP) treatment, this study was performed. Methods: Hep2 human laryngeal cancer cells were treated with various concentrations of MT and/or DDP in vitro for various times. Then cells proliferation was detected by CCK8 assays and cell apoptosis or cell cycle was assayed by flow cytometry. The coefficient of drug interaction (CDI) was used to evaluate whether MT could affect the sensitivity of Hep2 cells to DDP. Results:It was demonstrated by CCK8 assays that MT or DDP used alone inhibited the proliferation of Hep2 cells in a dosedependent manner.Combined treatment with MT and DDP synergistically inhibited the proliferation of Hep2 cells with the synergism between two drugs (CDI<1). Furthermore,flow cytometry results showed that MT promoted apoptotic cells and the proportion of cells in subG1 phase in Hep2 cells, and cotreatment with MT and DDP increased apoptotic cells (the apoptotic rate of cells in the 0.5 mmol/L MT and 20 μg/ml DDP combination group was significantly higher than that in 20 μg/ml DDP group, \[40.9±3.0\]% vs \[11.0±09\]%, P<0.01) and the proportion of cells in subG1 phase (the proportion of cells in subG1 phase in the 0.5 mmol/L MT and 20 μg/ml DDP combination group was significantly higher than that in 20 μg/ml DDP group, \[73.0±2.4\]% vs \[40.4±3.0\]%, P<0.01). Caspase inhibitor ZVADfmk reversed the suppression of Hep2 cell proliferation and the induction of Hep2 cell apoptosis by MT and/or DDP (both P<0.01). Conclusions:Our findings demonstrate that melatonin can induce Hep2 human laryngeal cancer cell apoptosis in caspasedependent manners, thereby synergistically enhancing the suppressive effects of cisplatin on human laryngealcancercellproliferation.
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Projects supported by the National Natural Science Foundation of China (No. 81502466), and the Medical and Health Research Foundation of Nanjing Military Area Command(No. 14MS023)