氧化白藜芦醇体内外抑制肝癌细胞增殖的研究

Study on anti-hepatocarcinoma activity and of mechanism of oxyresveratrol in vitro and in vivo

目的:研究氧化白藜芦醇对肝癌SMMC-7721细胞以及小鼠移植性肿瘤H22的抑制作用及其抗肝癌作用机制。方法:采用四甲基偶氮唑蓝(MTT)法检测氧化白藜芦醇对人肝癌SMMC-7721细胞体外增殖的抑制效果。流式细胞术测定肝癌SMMC-7721细胞的凋亡率。建立小鼠H22肝癌细胞移植瘤模型,分为对照组、环磷酰胺组、氧化白藜芦醇80、40、20 mg/kg剂量组,以实体瘤瘤块生长曲线及抑瘤率为指标评价氧化白藜芦醇对小鼠移植瘤生长的抑制作用;取用不同剂量组作用后的瘤块组织,采用免疫组织化学法检测Bax,bcl-2,Caspase-3蛋白表达情况。结论:MTT结果显示,氧化白藜芦醇对肝癌7721肿瘤细胞的IC50值为58.13μg/ml,抗肿瘤活性良好;流式细胞术结果显示氧化白藜芦醇促进肝癌7721细胞凋亡;体内试验显示氧化白藜芦醇对移植瘤的抑制作用明显,80、40、20 mg/kg三个剂量组对H22移植瘤抑制率为76.88%、65.90%和45.99%,呈一定量效关系,氧化白藜芦醇增加caspase-3表达量及Bax/Bcl-2比值。结论:氧化白藜芦醇具有明显的体内外抑制肿瘤作用,作用机制可能与诱导细胞凋亡有关。

Objective ：To investigate the inhibitory effect of oxyresveratrol on SMMC-7721 cell line and Hepatic cancer H22. To study the anti-hepa- tocarcinoma mechanism of oxyresveratrol in vitro and in vivo. Methods： MTT assay was used to detect the inhibitory effect of oxyresveratrol on human ＇hepatic cell line SMMC-7721 proliferation in vitro. Flow cytometry was used to assay the apoptosis rates of SMMC-7721 cells. Hepato- carcinoma H22 model was performed to observe the anti-hepatocarcinoma activity of oxyresveratrol in vivo. Animals were divided into five groups including： negative control group, CTX group and three groups treated with oxyresveratrol at the dose 80,40,20mg/kg. The inhibitory effect of oxyresveratrol in vivo was evaluated by tumor growth curve and inhibitory rates. The expressions of Bax, bcl-2 and Caspase-3 in tumor were detected by immunohistochemical staining. Results： MTT assays showed that the IC50 of oxyresveratrol for the hepatic cell line SMMC- 7721 was 58.13μg/ml. Oxyersveratrol of 80 ,40 ,20mg/kg had significant inhibitory effect and dose-related effect on growth of tumor,the in- hibitory rates of tumor were 76.88% （ P 〈 0.01 ） ,65.90% （ P 〈 0.05 ） and 45.99%. Oxyresveratrol can help to increase the expression of caspase-3 and the index of Bax/Bcl-2 in cells. Conclusion： Oxyresveratrol has obvious anti-tumor activities both in vivo and in vitro. The possible mechanism of anti-tumor action may be related to inducing cell apoptosis.