Kao S T, Yeh C C, Hsieh C C, Yang M D, Lee M R, Liu H S, Lin J G
China Medical College Hospital, China Medical College, Taichung, Taiwan.
Life Sci. 2001 Aug 17;69(13):1485-96. doi: 10.1016/s0024-3205(01)01226-7.
Bu-Zhong-Yi-Qi-Tang (BZYQT), a Chinese herbal medicine, inhibited the proliferation of human hepatoma cell lines (Hep3B, HepG2 and HA22T) dose-dependently. The IC50s of BZYQT on the proliferation of Hep3B, HepG2 and HA22T were 432.5+/-31.8 microg/ml, 455.4+/-24.2 microg/ml, and 2284.3+/-77.2 microg/ml respectively on day 3. However, BZYQT did not significantly inhibit the proliferation of normal human hepatocytes (Chang liver, CCL-13) at the concentration under 5,000 microg/ml. Major compounds of BZYQT, including astragaloside IV, ginsenoside Rb1 and Rg1, saikosaponin a and c, and glycyrrhizin, have been identified. To investigate the key inhibitors of BZYQT. Hep3B cells were treated with BZYQT, individual major compounds of BZYQT, and mixture of major compounds in the same ratio as present in BZYQT. Significant inhibition of proliferation was detected in BZYQT and its major compounds mixture in a comparable level. Not any individual major compound examined could suppress the proliferation of Hep3B cells. This data indicated that there could be synergistic or additive effects of the ingredients in BZYQT. BrdU incorporation, cell cycle analysis and DNA fragmentation assay revealed that BZYQT suppressed the proliferation of hepatoma cells via G0/G1 cell cycle arrest and inhibition of DNA synthesis followed by apoptosis.
补中益气汤(BZYQT)是一种中药,能剂量依赖性地抑制人肝癌细胞系(Hep3B、HepG2和HA22T)的增殖。第3天时,BZYQT对Hep3B、HepG2和HA22T增殖的IC50分别为432.5±31.8微克/毫升、455.4±24.2微克/毫升和2284.3±77.2微克/毫升。然而,在浓度低于5000微克/毫升时,BZYQT对正常人肝细胞(Chang liver,CCL - 13)的增殖没有显著抑制作用。已鉴定出BZYQT的主要成分,包括黄芪甲苷IV、人参皂苷Rb1和Rg1、柴胡皂苷a和c以及甘草酸。为了研究BZYQT的关键抑制剂,用BZYQT、BZYQT的各个主要成分以及与BZYQT中相同比例的主要成分混合物处理Hep3B细胞。在BZYQT及其主要成分混合物中检测到了相当程度的显著增殖抑制作用。所检测的任何单个主要成分都不能抑制Hep3B细胞的增殖。该数据表明BZYQT中的成分可能存在协同或相加作用。BrdU掺入、细胞周期分析和DNA片段化分析表明,BZYQT通过G0/G1期细胞周期阻滞和抑制DNA合成继而诱导凋亡来抑制肝癌细胞的增殖。