1,25(OH)2D3联合顺铂对原代肺腺癌细胞周期及调控因子的影响

Effects of 1,25(OH)2D3 combined with cisplatin on cell cycle and regulatory factors of primary cultured lung adenocarcinoma cells

目的:探讨1,25(OH)2D3联合顺铂对原代肺腺癌细胞周期及周期相关调控因子的影响。方法:体外培养手术切除的肺腺癌组织细胞,经药物作用后CCK-8法测定细胞抑制率,流式细胞仪检测细胞周期,RT-PCR检测细胞周期调控因子Cyclin D1、CDK4转录水平。结果:不同浓度的1,25(OH)2D3、顺铂单药作用于肺腺癌细胞均有明显的抑制作用,两药联合表现为协同作用,与单药相比,差异有统计学意义(P<0.05)。细胞周期分析显示,经药物联合处理后的肺癌细胞,G0/G1期细胞数增多,S期和G2/M期细胞减少。细胞周期调控因子Cyclin D1、CDK4转录水平均有所降低,差异有统计学意义(P<0.05)。结论:1,25(OH)2D3联合铂类抗癌药物抑制原代肺腺癌细胞的增殖能力、诱导细胞周期阻滞,与下调Cyclin D1和CDK4的表达有关。

Objective:To investigate the effects of 1,25(OH)2D3 combined with cisplatin on cell cycle and cell cycle-related regulatory factors in primary lung adenocarcinoma cells.Methods:Lung adenocarcinoma tissue cells were cultured in vitro.The cell inhibition rate was measured by CCK-8 assay after drug treatment.The cell cycle was detected by flow cytometry.The transcriptional levels of cell cycle regulators Cyclin D1 and CDK4 were detected by RT-PCR.Results:Different concentrations of 1,25(OH)2D3,cisplatin had obvious inhibitory effects on lung cancer cells.The combination of the two drugs showed synergistic effect,and there was significant difference compared with the single drug(P<0.05).Cell cycle analysis showed that G0/G1 cells increased and S and G2/M cells decreased after the lung cancer cells were treated by drug treatment.The transcriptional levels of cell cycle regulators Cyclin D1 and CDK4 were all decreased,and were statistically significant(P<0.05).Conclusion:1,25(OH)2D3 combined with platinum anticancer drugs inhibited the proliferation of primary lung adenocarcinoma cells and induced cell cycle arrest,which was associated with down-regulation of Cyclin D1 and CDK4 expression.