苯乙酸对肝癌细胞的抑制作用及其机制

目的：阐明苯乙酸(PA)对肝癌细胞系SSMC-7721细胞增殖的抑制作用及部分作用机制，探讨PA用于肝癌治疗的可行性。方法：以0.25、0.50、1.00、2.00和4.00 mmol·L^-1浓度的PA作用于对数生长期的肝癌细胞系SSMC-7721细胞，检测上述各浓度时PA在24、48和72 h对SSMC-7721细胞的抑制率。应用噻唑蓝(MTT)比色法，以0.25、0.50、1.00、2.00和4.00 mmol·L^-1的PA作用于SSMC-7721细胞，分别于24、48、72 h 对细胞增殖抑制率进行检测；流式细胞术检测2.00 mmol·L^-1PA作用36 h后的SSMC-7721细胞周期各时相的变化；使用透射电镜观察经2.00 mmol·L-1PA作用36 h后的SSMC-7721细胞超微结构的改变；用Caspase-3活性检测试剂盒检测经过和不经过PA作用的SSMC-7721细胞中Caspase-3活性的差异。结果：0.25、0.50、1.00、2.00和4.00 mmol·L^-1的PA均可以抑制SSMC-7721细胞生长,随着浓度递增24 h 细胞增殖抑制率为7.2%～73.1%，48 h 为9.1%～87.5%，72 h 为15.8%～91.9%，随PA浓度增加和作用时间延长，抑制率逐渐增加，2.00 mmol·L-1 PA 为最佳实验浓度；PA可使SSMC-7721细胞的G0/G1期和G2/M期细胞比例增加；PA可通过Caspase-3途径诱发SSMC-7721细胞凋亡,电镜下可观察到凋亡的特征性变化。结论：PA可有效抑制肝癌SSMC-7721 细胞的增殖，诱发细胞凋亡，Caspase-3活化是参与机制之一。

Suppression of phenylacetate on hepatic carcinoma line and its mechanism

Objective To study the inhibitory effect of phenylacetate(PA) on hepatic carcinoma cells for developing of gene therapy.Methods SSMC-7721 cells were treated with or without PA(0.25,0.50,1.00,2.00,4.00 mmol·L-1) for 24,48 and 72 h,respectively.The cellular proliferation inhibitory rate was evaluated by MTT assay.Flow cytometry was used to estimate the changes of cell cycle.The morphous of tumor cells suppressed by PA was observed with electronic microscope.Finally,the activity of Caspase-3 protein to estimate the way of apoptosis of SSMC-7721 cells under the control of PA was determined.Results The growth of SSMC-7721 cells were inhibited by 0.25-4.00 mmol·L-1 PA for 24-72 h.With the increase of concentration of PA,the proliferation inhibitory rate were 7.2%-73.1 % at 24 h,9.1%-87.5% at 48 h,15.8%-91.9% at 72 h.With the prolongation of treating time and the increasing of PA concentration,the inhibitory rate was increased.2.00 mmol·L-1 was the best concentration for the experiment.The cell cycle was arrested at G0 / G1 and G2/M phase.Some characteristic changes of apoptosis were observed by electronic microscope,the activity of Caspase-3 protein in SSMC-7721 mediated by PA was increased.Conclusion PA could effectively inhibit SSMC-7721 cell proliferation and induce the apoptosis.Caspase-3 protein at least partly participate in the mechanism.