目的：研究褪黑素（melatonin，MT）对人喉癌细胞增殖与凋亡的影响及MT增强人喉癌细胞对顺铂（cisplatin，DDP）治疗的敏感性。方法：采用不同质量浓度MT和DDP单独或联合处理Hep2细胞；通过CCK8法检测细胞增殖，流式细胞术检测细胞凋亡和细胞周期，采用两药相互作用指数（coefficient of drug interaction，CDI）评估MT是否影响Hep2细胞对DDP的敏感性。结果：CCK8检测结果显示，单用MT或DDP可浓度依赖性抑制Hep2细胞的增殖，MT可协同增强DDP对Hep2细胞的增殖抑制作用（CDI<1）。流式细胞术检测细胞凋亡和细胞周期结果显示，MT可促进Hep2细胞凋亡以及增加亚G1期细胞比例(P<0.01)，MT可协同DDP促进Hep2细胞凋亡\[0.5 mmol/L MT联合20 μg/ml DDP组的细胞凋亡率显著高于20 μg/ml DDP组，（40.9±3.0）% vs （11.0±0.9）%，P<0.01\]以及亚G1期细胞比例\[0.5 mmol/L MT联合20 μg/ml DDP组的亚G1期细胞比例显著高于20 μg/ml DDP组，(73.0±2.4)% vs (40.4±3.0)%，P<0.01\]。加入Caspase抑制剂ZVADfmk可逆转MT和/或DDP对Hep2细胞的增殖抑制作用和凋亡诱导作用（均P<0.01）。结论：MT能以Caspase依赖的方式诱导人喉癌细胞Hep2的凋亡，从而协同增强DDP对细胞的增殖抑制作用。

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: Hep2 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 CCK8 assays and cell apoptosis or cell cycle was assayed by flow cytometry. The coefficient of drug interaction (CDI) was used to evaluate whether MT could affect the sensitivity of Hep2 cells to DDP. Results：It was demonstrated by CCK8 assays that MT or DDP used alone inhibited the proliferation of Hep2 cells in a dosedependent manner.Combined treatment with MT and DDP synergistically inhibited the proliferation of Hep2 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 subG1 phase in Hep2 cells, and cotreatment 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 \[11.0±09\]%, P<0.01) and the proportion of cells in subG1 phase (the proportion of 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, \[73.0±2.4\]% vs \[40.4±3.0\]%, P<0.01). Caspase inhibitor ZVADfmk reversed the suppression of Hep2 cell proliferation and the induction of Hep2 cell apoptosis by MT and/or DDP (both P<0.01). Conclusions：Our findings demonstrate that melatonin can induce Hep2 human laryngeal cancer cell apoptosis in caspasedependent manners, thereby synergistically enhancing the suppressive effects of cisplatin on human laryngealcancercellproliferation.

国家自然科学基金资助项目（No. 81502466）；南京军区医药卫生科研基金资助项目（No. 14MS023）