蟾毒灵抗小鼠原位移植性肝癌整体药效学研究

Anti-tumor effects of bufalin on the orthotopic transplantation tumor model of hepatocellular carcinoma in mice

目的 探讨蟾毒灵对小鼠原位移植性肝癌的抗肿瘤作用。方法 建立肝原位移植瘤模型。随机分为 5组 ,每组 15只 ,蟾毒灵 3组分别给予 1.5、1.0、0 .5mg/kg体重 ,腹腔注射 ;生理盐水 (NS)组给予等体积的生理盐水 ,用法同蟾毒灵组 ;阿霉素 (ADM )组按 8mg/kg体重给药。用药后第 11天每组分别处死 10只荷瘤鼠 ,测量肿瘤大小 ,取瘤组织行病理学检查和瘤细胞超微结构观察。剩余各组观察带瘤生存期。结果 蟾毒灵组肿瘤大小均较NS组明显缩小 (P <0 .0 1) ;中、大剂量的蟾毒灵组带瘤生存期较NS组明显延长 (P <0 .0 5 ,P <0 .0 1)。大、中剂量的蟾毒灵瘤组织以中重度坏死为主 ,小剂量以轻中度坏死为主。电镜下大、中剂量蟾毒灵组可见肿瘤细胞凋亡征象。结论 蟾毒灵对小鼠原位移植性肝癌有显著的抗肿瘤作用 ,诱导肿瘤细胞凋亡可能是蟾毒灵的抗肿瘤机理之一。

Objective To investigate anti tumor effects of bufalin to the orthotopic transplantation tumor model of hepatocellular carcinoma in mice.Methods Orthotopic transplantation tumor models of hepatocellular carcinoma were established on mice.Seventy five models were randomly divided into 5 groups ( n =15 in each group).Bufalin were injected imtraperitoneally into the 3 groups at doses of 1.5,1.0、0.5 mg/kg respectively.NS group was injected with equal volume of saline as above and adriamycin was injected intraperitoneally at a dose of 8.0 mg/kg.Ten mice in each group were killed after administration and tumor tissues were examined by pathology and electron microscopy.The survival time in each group was observed.Results The tumor volume in each group of bufalin was reduced significantly (compared with NS group, P < 0.01), and the survival time prolonged in group Buf1 and Buf2 (compared with NS group, P < 0.05 and P < 0.01, respectively).Mainly moderate or severe necrosis was found in tumor tissues.Apoptosis characteristics could be seen in tissues of group Buf1 and Buf2.Conclusion Bufalin has significant anti tumor effects on the orthotopic transplantation tumor model of hepatocellular carcinoma in mice.Induction of apoptosis of tumor cells might be one of the anti tumor mechanisms of bufalin.