Wang Chun-lei, Wan Yuan-lian, Liu Yu-cun, Huang Zhi-qiang
Department of General Surgery, the First Hospital, Peking University, Beijing 100034.
Chin Med Sci J. 2006 Mar;21(1):33-5.
To determine whether transforming growth factor betal (TGF-beta1)/Smad signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines.
Three human hepatic carcinoma cell lines, HepG2, Huh-7, and Hep3B, were used in this study. TGF-beta1-induced apoptosis in hepatic carcinoma cell lines was analyzed using TUNEL assay. For identifying the mechanism of apoptosis induced by TGF-beta1, cell lines were transfected with a TGF-beta1-inducible luciferase reportor plasmid containing Smad4 binding elements. After transfection, cells were treated with TGF-beta1, then assayed for luciferase activity.
The apoptosis rate of HepG2 cell lines (48.51% +/- 8.21%) was significantly higher than control (12.72% +/- 2.18%, P <0.05). But TGF-beta1 was not able to induce apoptosis of Huh-7 and Hep3B cell lines. The relative luciferase activity of TGF-beta1-treated HepG2 cell lines (4.38) was significantly higher than control (1.00, P < 0.05). But the relative luciferase activity of TGF-beta1-treated Huh-7 and Hep3B cell lines less increased compared with control.
HepG2 cells seem to be highly susceptible to TGF-beta1-induced apoptosis compared with Hep3B and Huh-7 cell lines. Smad4 is a central mediator of TGF-beta1 signaling transdution pathway. TGF-beta1/Smad signaling pathway might mediate p53-dependent apoptosis in hepatoma cell lines.
确定转化生长因子β1（TGF-β1）/Smad信号通路是否介导肝癌细胞系中p53依赖的细胞凋亡。
本研究使用了三种人肝癌细胞系，HepG2、Huh-7和Hep3B。采用TUNEL法分析TGF-β1诱导的肝癌细胞系凋亡情况。为了确定TGF-β1诱导凋亡的机制，用含有Smad4结合元件的TGF-β1诱导型荧光素酶报告质粒转染细胞系。转染后，用TGF-β1处理细胞，然后检测荧光素酶活性。
HepG2细胞系的凋亡率（48.51%±8.21%）显著高于对照组（12.72%±2.18%，P<0.05）。但TGF-β1不能诱导Huh-7和Hep3B细胞系凋亡。TGF-β1处理的HepG2细胞系的相对荧光素酶活性（4.38）显著高于对照组（1.00，P<0.05）。但TGF-β1处理的Huh-7和Hep3B细胞系的相对荧光素酶活性与对照组相比增加较少。
与Hep3B和Huh-7细胞系相比，HepG2细胞似乎对TGF-β1诱导的凋亡高度敏感。Smad4是TGF-β1信号转导通路的中心介质。TGF-β1/Smad信号通路可能介导肝癌细胞系中p53依赖的细胞凋亡。
