中药复方四味肝泰对荷瘤小鼠和HepG2肝癌细胞的影响

Effects of Traditional Chinese Medicine Prescription Si-Wei-Gan-Tai on Tumor-burdened Mice and Human Hepatocellular Liver Carcinoma Cell Line

目的:阐明中药复方四味肝泰对肝癌荷瘤小鼠和人体肝癌细胞(HepG2)的抗肝癌作用。方法:首先对昆明小鼠腋下注射小鼠肝癌细胞H22,建立肝癌荷瘤小鼠模型,并检测给药后荷瘤小鼠的肿瘤抑制率,对药物的抗肝癌作用进行评价;然后采用实时荧光定量PCR对荷瘤小鼠实体瘤中凋亡基因(Bax和Bcl-2)的表达进行分析。并用高通量药物筛选仪测定给药培养的人体肝癌细胞(HepG2)的细胞增殖与细胞周期。结果:四味肝泰能够抑制荷瘤小鼠实体瘤的生长,其抑瘤率为47.79%,瘤组织中Bax/Bcl-2的基因表达比值高于模型对照组;四味肝泰能够抑制肝癌细胞的增殖;当作用浓度大于500μg.mL-1时,四味肝泰使细胞周期停滞在G2/M期。结论:四味肝泰具有较好的抗肝癌作用,其可能通过Bax/Bcl-2调控肝癌细胞凋亡,阻滞细胞周期,从而达到抑制肝癌细胞恶性增殖的目的。

This study was aimed to evaluate the anti-tumor effects of Si-Wei-Gan-Tai （SWGT） on the transplantable tu- mor in mice and human hepatocellular liver carcinoma cell line （HepG2）. Firstly, the tumor-burdened mice model （TBM） was established through injecting the hepatorna cell line 22 （H22） into the armpits of mice. And the anti-tumor effects of SWGT were evaluated by determining the inhibition rate on transplant tumor in the TBM after drug administration. Ex- pression of apoptotic genes, Bax and Bcl-2, on transplantable tumor in the TBM were thereafter determined by real-time quantitative fluorescence polymerase chain reaction （PCR）. Furthermore, the cell growth and cell cycle of HepG2 ceils treated with SWGT were detected by high throughput screening （HTS）. The results manifested that the inhibition rate of tumor was 47.79%, and the Bax/Bcl-2 ratio in transplantable tumor treated with SWGT was higher than that in the model group, which indicated that the growth of transplantable tumor in TBM can be inhibited by SWGT. Moreover, when the concentration of SWGT was higher than 500 Ixg/mL, there was an arrest of cell cycle progression on G2/M period, which suggested that the proliferation of HepG2 can also be inhibited by SWGT. In conclusion, SWGT had potent anti-tumor ef- fect, the mechanisms of which might he increasing the apoptosis of hepatoma cell and blocking the cell cycle through reg- ulating Bax/Bcl-2, to finally inhibit the malignant progression of the hepatoma cell.