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目的探讨亚硒酸钠、顺铂(Cisplatin,DDP)联用对体外培养的人肺腺癌A549细胞增值的抑制作用及其作用机制。方法将亚硒酸钠与DDP应用于A549 24 h后,用MTT法检测对细胞增殖的抑制作用效应;用FCM技术检测对细胞周期的影响;用HE染色技术观察细胞凋亡状态。结果 亚硒酸钠与DDP的联合效应值均大于1.15,二者之间有交互作用,P<0.01。DDP使A549细胞周期阻滞于S期、中高剂量组的亚硒酸钠使A549细胞周期阻滞于G0/G1期而发挥一定的抑瘤效应;二者联用后,中高联合剂量组的S期细胞分别由6.07%增至48.47%、由16.07%提高到30.57%,而G2/M期细胞则分别由17.12%降到8.23%、由14.86%降到5.30%。亚硒酸钠与顺铂联合组可见有胞核致密浓缩的细胞凋亡小体。结论在该实验条件下,亚硒酸钠与顺铂联用可显著增加对A549细胞增殖的抑制作用,通过将A549细胞周期阻滞于S期而发挥较强的抑瘤效应。二者之间存在较强的协同交互作用。诱导A549细胞凋亡及阻滞细胞周期进程可能是亚硒酸钠与DDP协同增效作用的机制。
Objective To investigate the inhibitory effect of sodium selenite and cisplatin (DDP) on the proliferation of human lung adenocarcinoma A549 cells cultured in vitro and its mechanism. Methods After sodium selenite and DDP were applied to A549 for 24 h, the inhibitory effect on cell proliferation was detected by MTT assay. The effect of sodium selenite and DDP on cell cycle was detected by FCM and the apoptosis was observed by HE staining. Results The combined effect of sodium selenite and DDP was greater than 1.15, with an interaction between them (P <0.01). DDP blocked A549 cell cycle in S phase, while sodium selenite in medium and high dose group blocked A549 cell cycle in G0 / G1 phase and exerted certain antitumor effect. The number of senescent cells increased from 6.07% to 48.47%, from 16.07% to 30.57%, while the percentage of G2 / M phase decreased from 17.12% to 8.23%, from 14.86% to 5.30% respectively. Sodium selenite combined with cisplatin group can be seen dense condensed nuclei apoptotic bodies. Conclusion Under the experimental conditions, sodium selenite combined with cisplatin can significantly increase the inhibition of A549 cell proliferation, A549 cell cycle arrest in the S phase and play a strong anti-tumor effect. There is a strong synergistic interaction between the two. Induction of A549 cell apoptosis and arrest of cell cycle progression may be synergistic mechanism of sodium selenite and DDP.