5-杂氮-2′-脱氧胞苷联合苯丁酸钠对人结肠癌细胞HT29的抑制作用

目的:探讨DNA甲基化抑制剂5-杂氮-2′-脱氧胞苷(5-aza-2dC)联合组蛋白脱乙酰化酶抑制剂苯丁酸钠(SPB)的抗肿瘤效应及其机制。方法:将HT29细胞分为:对照组、SPB(1mmol/L)处理组、5-aza-2dC(10μmol/L)处理组、5-aza-2dC(10μmol/L)+SPB(1mmol/L)处理组。MTT法测定各处理组细胞的生存曲线,流式细胞仪检测各组细胞的凋亡率和细胞周期。结果:生长曲线结果提示:5-aza-2dC和SPB均能抑制HT29细胞的生长增殖,但差异不明显,联合应用后,细胞增殖得到明显抑制;流式细胞术检测细胞凋亡结果显示:SPB、5-aza-2dC、SPB+5-aza-2dC处理HT29后,细胞凋亡率分别为11.32%、20.25%和42.37%,三者比较有统计学差异(P<0.05);细胞周期分布检测显示:与对照组相比,单用SPB处理细胞,细胞周期分布变化不明显,5-aza-2dC处理细胞后,59.02%的细胞周期阻滞在G1期,而SPB联合5-aza-2dC后,S期细胞比例明显减少,G1期细胞比例可达73.7%,4组比较差异有统计学意义(P<0.05)。结论:5-杂氮-2′-脱氧胞苷联合苯丁酸钠可通过抑制细胞增殖、诱导细胞凋亡和细胞周期阻滞发挥抗肿瘤作用。

Inhibition of 5-aza-2'-deoxycytidine Combined Sodium Phenylbutyrate on Human Colon Cancer Cell Lines HT29

Objective To investigate the antitumor effects of DNA methylation inhibitor（5-aza-2＇-deoxycytidine,5-aza-2dC） combined histone deacetylase inhibitor（sodium phenylbutyrate,SPB） on human colon cancer cells and its possible mechanism.Methods The HT29 cells were divided into control group,SPB（1 mmol/L）group,5-aza-2dC （10 μmol/L） group and 5-aza-2dC （10 μmol/L）＋ SPB（1 mmol/L） group.The survival curve was tested by MTT assay and the apoptotic ratio and cell cycles were measured by flow cytometry.Results The survival curve indicated that the proliferation of HT29 could be inhibited with single 5-aza-2dC or SPB,but very significant difference of inhibition with control group was observed in combined group;the apoptotic ratio of three groups were 11.32%,20.25%,42.37% respectively,and they were significant difference（P0.05）;Compared with control group,the cell cycle of SPB group had no obvious change,59.02% cells of 5-aza-2dC group was blocked at phase G1,but in combined group the rate of cells at phase S was significantly decreased,the rate of cells at phase G1 was high to 73.7% （P0.05）. Conclusion 5-aza-2dC combined SPB could effectively antitumor through inhibiting HT29 proliferation,inducing apoptosis and blocking the cell cycles.