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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 investigate the effects of sodium 4-phenylbutyrate (SPB) and all-trans retinoic acid (ATRA), a histone deacetylase inhibitor, on the proliferation of cervical cancer cell lines Hela growth and invasion ability to explore the effect of sodium phenylbutyrate and all-trans retinoic acid combination. Methods Hela cells were cultured in vitro and divided into 4 groups according to different treatment factors: group A: control group, PBS solution (1 ml); group B: 1 μmol / L ATRA monotherapy group; group C: 1 mmol / L SPB single drug treatment group; D group 1μmol / L ATRA + 1 mmol / LSPB treatment group. Cell growth curve, MTT colorimetric assay and cell clone formation assay were used to observe the inhibition of cell growth. Cell cycle distribution was measured by flow cytometry. Transwell chamber assay Changes in cell invasiveness. Results Compared with the control group and the single drug group, the growth of Hela cells in ATRA and SPB groups was significantly slower than that in control and SPB groups (80.37%, P <0.05). The cell cycle was arrested at G0 / The number of cells in G1 phase and S phase decreased. The invasive ability of cervical cancer cell line Hela after drug treatment decreased compared with control group and single drug group (P <0.05). Conclusion Histone deacetylase inhibitor sodium phenylbutyrate and all-trans retinoic acid combination has obvious synergistic effect.