苯丁酸钠和全反式维甲酸对宫颈癌细胞株Hela的影响

Effect of sodium 4-phenylbutyrate and all transretinoic acid on cervical cancer Hela cell line

目的研究组蛋白去乙酰化酶(histone deacetylase,HDAC)抑制剂苯丁酸钠(Sodium 4-Phenylbutyrate,SPB)和全反式维甲酸(all transretinoic acid,ATRA)单独及联合运用对宫颈癌细胞株Hela生长及侵袭能力的影响,探讨苯丁酸钠和全反式维甲酸联用的效果。方法体外培养宫颈癌细胞株Hela细胞,根据处理因素不同分为4组,A组:对照组,PBS液(1ml)处理组;B组:1μmol/L ATRA单药处理组;C组:1 mmol/L SPB单药处理组;D组1μmol/L ATRA+1 mmol/LSPB处理组。应用细胞生长曲线、四甲基偶氮唑蓝(MTT)比色法、细胞克隆形成试验观察细胞生长的抑制作用;采用流式细胞术测定细胞周期分布的变化;用Transwell小室法检测药物处理前后细胞侵袭力的变化。结果与对照组、单用药组相比,ATRA和SPB联用时宫颈癌细胞株Hela细胞的生长速度明显减慢,克隆形成抑制率达80.37%(P<0.05),细胞周期被阻滞在G0/G1期,S期细胞数减少;药物处理后宫颈癌细胞株Hela的侵袭能力降低,和对照组、单用药组相比,差异有统计学意义(P<0.05)。结论组蛋白去乙酰化酶抑制剂苯丁酸钠和全反式维甲酸联用时有明显的增效作用。

Objective To study the effect of sodium 4-phenylbutyrate（SPB） and all transretinoic acid（ATRA）,two histone deacetylase inhibitors,on invasion ability of cervical cancer Hela cells.Methods Cervical cancer Hela cells cultured in vitro were divided into groups A-D as 1 ml PBS treatment group（control group）,1 μmol/L ATRA treatment group,1 mmol/L SPB treatment group,and 1 μmol/L ATRA plus 1 mmol/L SPB treatment group,respectively.Cell growth curve,MTT and clonogenic assay in vitro were used to observe the inhibitory effects of SPB and ATRA on cell proliferation.Distribution of cell cycles was detected by flow cytometry,and invasion ability of Hela cells was determined by Transwell chamber assay.Results The growth of Hela cells was significantly slower in 1 μmol/L ATRA ＋1 mmol/L SPB treatment group than in control and 1 μmol/L ATRA treatment group or 1 mmol/L SPB treatment group,with an inhibition rate of colony formation of 80.37%（P0.05）.The cell cycle was arrested at the G0/G1 phase,the number of cells in S phase was decreased after combined treatment with SPB with ATRA.The invasion ability of Hela cells was significantly weaker in 1 μmol/L ATRA ＋1 mmol/L SPB treatment group than in control group and 1 μmol/L ATRA treatment group or 1 mmol/L SPB treatment group（P0.05）.Conclusion SPB and ATRA used in combination have an obvious synergistic effect on the invasion ability of cervical cancer Hela cells.