Melatonin combined with cisplatin suppresses proliferation of human glioma cells U251 and SHG-44 by inducing cell apoptosis
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Abstract:
Objective : To investigate the effect of melatonin (MT) and cisplatin (DDP) used alone or in combination on proliferation and apoptosis of human glioma cells U251 and SHG-44. Methods: U251 and SHG-44 cells were treated with various concentrations of MT and DDP alone or in combination, and the control group (without adding any drug) and ethanol group (adding the ethanol) were included. CCK-8 assay was used to detect cell proliferation, and flow cytometry was used to detect cell apoptosis and cell cycle. The coefficient of drug interaction (CDI) was used to evaluate whether MT could affect the sensitivity of U251 and SHG-44 cells to DDP. Results: CCK-8 results showed that MT or DDP used alone inhibited the proliferation of U251 and SHG-44 cells in a concentration dependent manner, and 0.5 mmol/L MT synergistically enhanced the proliferation inhibitory effect of DDP on U251 and SHG-44 cells (CDI<1). Flow cytometry results showed that MT promoted U251 and SHG-44 cell apoptosis, and MT enhanced the apoptosis inducing effect of DDP on U251 and SHG-44 cells. The apoptotic rate of U251 and SHG-44 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 (\[66.3±1.0\]% vs \[45.9±1.7\]%, \[355±0.8\]% vs \[15.5±08\]%, P<0.01). And the percentage of U251 and SHG-44 cells in sub-G1 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 (\[524±2.1\]% vs \[27.9±1.5\]%, \[39.7±1.5\]% vs \[27.7±1.3\]%, P<0.01\]. Conclusion: MT can enhance the apoptosis inducing effect of DDP on human glioma cells U251 and SHG-44, thereby synergistically enhancing the suppressive effects of DDP on human glioma cell proliferation, which may be used as a complementary drug in human glioma chemotherapy.
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Project supported by the National Key Basic Research Development Program (973 Program) of China (No. 2005CB523304)