黄芩素对肝癌H22荷瘤小鼠的抑瘤作用研究

目的:研究黄芩素对肝癌H22荷瘤小鼠的抑瘤作用。方法:以H22肝癌细胞接种于正常小鼠左前肢腋窝皮下复制肝癌H22荷瘤模型。实验分为模型对照、环磷酰胺(30mg·kg-1)和黄芩素高、中、低剂量(80、40、20mg·kg-1)组。灌胃给药,每天1次,连续15d。末次给药后处死小鼠,剥离完整的肿瘤组织称重,并计算肿瘤抑制率;流式细胞仪分析细胞周期分布和凋亡率;按试剂盒说明书测定肿瘤组织中半胱氨酸蛋白酶(Caspase)-3的活性;RT-PCR测定瘤组织中B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)的mRNA表达水平。结果:高、中剂量黄芩素可显著抑制模型小鼠体内肿瘤生长(P<0.01或P<0.05),抑制率分别为61.63%和44.65%;可显著提高G0/G1期细胞百分比(P<0.05),并减少S期细胞(P<0.01或P<0.05)。与模型对照组比较,黄芩素高、中、低剂量组细胞凋亡率显著提高(P<0.01或P<0.05)。高、中剂量黄芩素可显著增强肿瘤组织中Capcase-3活性(P<0.01或P<0.05),抑制Bcl-2mRNA表达(P<0.01或P<0.05);高剂量黄芩素可显著提高肿瘤组织中BaxmRNA表达(P<0.05)。结论:黄芩素可促进肝癌H22荷瘤小鼠肿瘤细胞的凋亡,其机制可能与增强Capcase-3活性、提高Bax表达,并抑制Bcl-2表达有关。

Anti-tumor Effects of Baicalein on H22 Hepatocarcinoma-bearing Mice

OBJECTIVE： To investigate the anti-tumor effects of baicalein on H22 hepatocarcinoma-bearing mice. METHODS： H22 tumor-bearing mice model was induced by H22 cell vaccination in normal mouse forelimb left axillary subcutaneous. H22 hepa- tocarcinoma-bearing mice model was induced and randomized into 5 groups： model control group, cytoxan group （30 mg. kg^-1）, baicalein high-dose,medium-dose and low-dose groups （80,40,20 mg.kg^-1）. They were given medicine intragastrically once a day for consecutive 15 days. After the last administration, all mice were sacrificed for weighing the tumor and calculating the tumor in- hibition rate. The cell cycle and the apoptosis rate were analyzed by flow cytometry. The activity of Caspase-3 was detected by a commercial kit. The mRNA expression levels of Bax and Bcl-2 were measured by RT-PCR. RESULTS： High-dose and medi- um-dose baicalein （80,40 mg. kg^-1） could inhibit the growth of tumor in model mice significantly（P〈0.01 or P〈 0.05） with inhibi- tion rates of 61.63% and 44.65% respectively; the ratio of FCM G0/G1 cells in high-dose and medium-dose baicalein （80,40 mg. kg^-1） groups was significantly increased （P〈0.01 or P〈0.05）, and the ratio of FCM S cells was significantly reduced （P〈0.05）. Compared with model control group, the apoptosis rates in baicalein low-dose, medium-dose and high-dose groups were increased significantly（P〈0.01 or P〈0.05）.The activity of Caspase-3 in medium-dose and high-dose groups and the mRNA expression levels of Bax in high-dose groups were increased significantly, and the mRNA expression of Bcl-2 in medium-dose and high-dose groups was decreased in baicalein groups. CONCLUSION： Baicalein is able to promote the apoptosis of tumor cells in mice, and the mechanism maybe involved in enhancing the activity of Caspase-3, increasing the mRNA expression of Bax and decreasing the mRNA expression of Bcl-2.