苦参素对实验性肝癌PCNA、cyclinD1、CDK4 表达的影响

目的: 研究苦参素对2-乙酰氨基芴(2-AAF)诱发大鼠实验性肝癌的防治作用, 并探讨其抑制肝癌细胞增殖的机制。方法: 以2-AAF 喂饲SD 大鼠制备肝癌模型。给予不同剂量的苦参素腹腔注射,观察肿瘤生成状况;免疫组化方法检测增殖细胞核抗原(PCNA) 蛋白的表达;RT-PCR 检测细胞周期素D1(cyclin D1)、细胞周期蛋白依赖激酶4(CDK4) mRNA的表达。结果: 苦参素各防治组大鼠肝表面癌结节数明显低于模型组, 预防组肝表面结节数最少。苦参素各预防治疗组PCNA 和cyclinD1、CDK4 的表达显著低于模型组(P <0.01) 。结论: 苦参素有预防或延缓2-AAF 诱发大鼠肝癌发生的作用, 其机制可能通过抑制cyclin D1、CDK4 mRNA 和PCNA 蛋白的表达, 从而诱导细胞周期阻滞, 抑制肝癌细胞过度增殖。

Effects of kwoninone on expression of PCNA,cyclin D1 and CDK4 in experimental hepatocellular carcinoma

AIM: To investigate the preventive and therapeutic effects of kwoninone on experimental hepatocellular carcinoma induced by 2-AAF and the mechanisms of its effects on cell proliferation.METHODS: Animal model of hepatocellular carcinoma was established by feeding SD rats with 0.05 % 2-AAF.Different doses of kwoninone were injected intraabdominally to observe the effects on occurrence of cancerous nodules.The expression of PCNA was observed by immunohistochemistry. The expression of cyclin D1 and CDK4 were detected by RT-PCR method.RESULTS: The cancerous nodules in preventive and therapeutic groups were significantly lower than that in model group and the cancerous nodules of preventive group were the lowest.The expression of cyclin D1 and CDK4 in preventive and therapeutic groups were significantly lower than that in model groups (P <0.01). CONCLUSION: Kwoninone can prevent or postpone hepatocarcinogenisis of hepatocellular carcinoma induced by 2-AAF.Kwoninone inhibits proliferation of liver cancer cells by inhibiting the expression of PCNA, cyclin D1 and CDK4 and inducing cell cycle arrest.