Aim To investigate the inhibitory effect of resveratrol ( Res ) on proliferation of rat hepatocellular carcinoma( HCC)though down-regulation of MLCK expression.Methods HCC model rats were induced by oral 0.9 mmol·L-1 DENA for 10 weeks.After 20 weeks, the treatment rats were intramuscularly injected with 50 mg·kg-1 resveratrol per day for 6 weeks.At the end of the study ( 26 weeks ), the rats were sacrificed and hepatoma nodules were counted, body weight, liver weight, the ratio of liver/body weight were recorded, the serum was determined and the pathological changes of the livers were observed; The effects of resveratrol on MLCK expression were examined by western blot and immunohistochemistry and resveratrol induced liver tumor cell apoptosis was examined by cell apoptosis detection kit.Results In the resveratrol-treated group, the body weight of rats were larger, the number of hepatoma nodules, the ratio of liver/body weight and serum AFP were smaller or lower significantly than in model group( P < 0.05 ).The hepatic tissues obtained from only oral DENA-treated rats showed a remarked increase in the levels of MLCK protein , but treatment with resveratrol reversed the levels of MLCK overexpression and induced liver tumor cell apoptosis.Conclusions The results indicate that resveratrol effectively inhibits DENA- induced liver tumor cell proliferation though down- regulation of MLCK expression level in rats .%目的 研究白藜芦醇(Res)通过影响肌球蛋白轻链激酶(MLCK)在肝脏中表达水平抑制原发性肝癌的增生.方法采用口服饮水中含0.9 mmol·L-1二乙基亚硝胺10周诱发原发性肝肿瘤;20周后,治疗组大鼠每天给予肌肉注射Res 50 mg·kg-1 6周;26周后,处死大鼠,计数肝表面癌结节数,称量和计算体重、肝重,肝/体重比,测定血清中甲胎蛋白的变化,观察大鼠肝脏的病理改变;用免疫组化和Western blot法检测Res对MLCK的表达影响,用细胞凋亡试剂盒检测Res诱导肿瘤细胞的凋亡.结果 Res治疗组大鼠和模型组大鼠相比,体重增加,肝肿瘤结节数和肝/体重比和血清甲胎蛋白值减少或降低(P<0.05).模型组大鼠肝组织MLCK的表达水平明显增加,而Res治疗可逆转MLCK的过表达水平,并诱导肿瘤细胞凋亡.结论 Res通过下调肝组织MLCK的表达水平诱导凋亡,抑制大鼠肝肿瘤细胞的增生.
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