大黄素对化疗药诱导肝癌细胞凋亡的增强作用

目的 观察大黄素对化疗药5-氟尿嘧啶（5-Fu）诱导肝癌细胞HepG2凋亡的影响。方法 不同浓度大黄素单用或与5-Fu联合作用HepG2细胞，以流式细胞仪（FCM）及末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）法检测细胞凋亡；免疫组织化学（sP）法检测Bax、Bcl-2、凋亡诱导因子（AIF）蛋白表达的改变。结果 2、4μg／m1大黄素分别与5-Fu联用，作用细胞16、24、48h后，时间依赖性地诱导HepG2细胞凋亡，且随大黄素浓度的增加细胞凋亡率有增加的趋势。联用组细胞凋亡率及Bax、Bcl-2、AIF蛋白表达与5-Fu单用组相比差异均有极显著性意义（均P〈0．01）。各组细胞凋亡率与Bax蛋白表达呈正相关（r=0．881，P〈0．05），与Bcl-2蛋白表达呈负相关（r=-0．942，P〈0．01），与AIF蛋白表达呈正相关（r=0．900，P〈0．05）。结论 大黄素可显著增强5-Fu诱导HepG2细胞凋亡的作用，可能与调控Bax、Bcl-2、AIF蛋白表达有关。

Effect of Emodin on Chemotherapeutic Drugs-induced Apoptosis in Human Hepatocellular Carcinoma Cells

Objective To study the effect of emodin on 5-fluorouracil(5-Fu)-induced apoptosis in human hepatocellular carcinoma cell line HepG2.Methods Flow cytometry(FCM) and terminal deoxynucleotidy1 transferase-mediated dUTP nick end labeling(TUNEL) were used to detect apoptosis after treatment with 5-Fu alone or in combination with various concentrations of emodin.Immunohistochemistry was used to analyze the changes of Bax,Bcl-2 and apoptosis-inducing factor(AIF) protein.Results Various concentrations of emodin combined with 5-Fu induced apoptotic responses in HepG2 cells in a time-dependent manner and the ratio of apoptotic cells had an incremental tendency with increases of concentrations of emodin.The ratio of apoptotic cells and expression levels of Bax and AIF protein in the combination group of emodin and 5-Fu were significantly higher than those of 5-Fu group,respectively,while the expression level of Bcl-2 protein was significantly reduced.Conclusion Emodin combined with 5-Fu sensitized HepG2 cells to 5-Fu-induced apoptosis in a time-dependent manner.The synergic effect may be associated with the regulation of expression levels of Bax,Bcl-2 and AIF protein.