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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20μg/ml DDP组的细胞凋亡率显著高于20μg/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20μg/ml DDP组的亚G1期细胞比例显著高于20μg/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: To investigate the effects of melatonin (MT) on the proliferation and apoptosis of human laryngeal carcinoma cells and MT sensitivity to cisplatin (DDP) treatment. Methods: Hep-2 cells were treated with different concentration of MT and DDP alone or in combination. Cell proliferation was detected by CCK-8 assay. Apoptosis and cell cycle were detected by flow cytometry. The co-efficient of drug interaction, CDI) to assess whether MT affects the sensitivity of Hep-2 cells to DDP. Results: The results of CCK-8 showed that MT alone or DDP could inhibit the proliferation of Hep-2 cells in a concentration-dependent manner, and MT synergistically enhanced the inhibitory effect of DDP on Hep-2 cells (CDI <1). The results of flow cytometry showed that MT could promote the apoptosis of Hep-2 cells and increase the proportion of cells in sub-G1 phase (P <0.01), and MT could cooperate with DDP to promote the apoptosis of Hep-2 cells [0.5 mmol / L MT combined with 20μg / ml DDP group was significantly higher than that of 20μg / ml DDP group (40.9 ± 3.0)% vs (11.0 ± 0.9)%, P <0.01] / L MT combined with 20μg / ml DDP group was significantly higher than that of 20μg / ml DDP group (73.0 ± 2.4)% vs (40.4 ± 3.0)%, P <0.01]. The addition of Caspase inhibitor Z-VAD-fmk reversed the proliferation and apoptosis-inducing effects of MT and / or DDP on Hep-2 cells (all P <0.01). CONCLUSION: MT can induce apoptosis of Hep-2 cells in a caspase-dependent manner and synergistically enhance the inhibitory effect of DDP on cell proliferation.