Chen Ching-Hsein, Huang Tien-Shang, Wong Chung-Hang, Hong Chian-Lang, Tsai Yung-Hong, Liang Chia-Ching, Lu Fung-Jou, Chang Wen-Huei
Graduate Institute of Biomedical and Biopharmaceutical Sciences, College of Life Sciences, National Chiayi University, 300 Syuefu Road, Chiayi 600, Taiwan.
Food Chem Toxicol. 2009 Mar;47(3):638-44. doi: 10.1016/j.fct.2008.12.024. Epub 2008 Dec 25.
This study investigated the effect of baicalein, silymarin, and their combination, on two human liver-derived cell lines, HepG2 (hepatocellular carcinoma) and Chang liver (non-tumor liver cells). It was found that 6.75 microg/ml baicalein or 100 microg/ml silymarin alone significantly inhibited the growth of HepG2. When baicalein was used in combination with silymarin on HepG2, an additive effect at 24 h and a synergistic effect at 48 h were observed. The viability at 48 h was 85.62% from 6.75 microg/ml baicalein treatment; but the viability reduced to 49.67%, 38.56%, and 19.61% when 25, 50, and 100 microg/ml silymarin respectively, was added to the treatment. By contrast, each treatment had little or no effect on Chang liver. Compared to treatment of baicalein or silymarin alone on HepG2, combination of both drugs synergistically increased the percentages of cells in G0/G1 phase and decreased those in S-phase, which were associated with up-regulation of Rb, p53, p21(Cip1) and p27(Kip1) and down-regulation of cyclin D1, cyclin E, CDK4 and phospho-Rb. The results indicate that the combination of baicalein and silymarin eradicates tumor cells efficiently, has minimal deleterious effects to the surrounding normal cells, and offers mechanistic insight for further exploitation of HCC treatment.
本研究调查了黄芩素、水飞蓟素及其组合对两种人肝源细胞系HepG2（肝癌细胞）和Chang liver（非肿瘤肝细胞）的影响。结果发现，单独使用6.75μg/ml黄芩素或100μg/ml水飞蓟素可显著抑制HepG2细胞的生长。当黄芩素与水飞蓟素联合用于HepG2细胞时，在24小时观察到相加作用，在48小时观察到协同作用。6.75μg/ml黄芩素处理48小时后的细胞活力为85.62%；但当分别添加25、50和100μg/ml水飞蓟素时，细胞活力分别降至49.67%、38.56%和19.61%。相比之下，每种处理对Chang liver细胞几乎没有影响或没有影响。与单独使用黄芩素或水飞蓟素处理HepG2细胞相比，两种药物联合使用可协同增加G0/G1期细胞的百分比，并降低S期细胞的百分比，这与Rb、p53、p21(Cip1)和p27(Kip1)的上调以及细胞周期蛋白D1、细胞周期蛋白E、细胞周期蛋白依赖性激酶4和磷酸化Rb的下调有关。结果表明，黄芩素和水飞蓟素的组合可有效根除肿瘤细胞，对周围正常细胞的有害影响最小，并为进一步开发肝癌治疗方法提供了机制方面的见解。
