目的 研究苦参碱对人肝癌细胞HepG2荷瘤裸鼠的抑瘤作用及其作用机制。方法 BALB/C裸鼠随机分为对照组和苦参碱25、50、75 mg/kg组,每组各10只。建立裸鼠肝癌细胞HepG2移植瘤模型。对照组ip生理盐水1 mL,1次/d;苦参碱25、50、75 mg/kg组分别ip 0.5、1.0、1.5 mg/mL苦参碱溶液1 mL,1次/d。连续给药35 d。计算瘤体体积和肿瘤体积抑制率。观察裸鼠瘤体HE染色病理改变和免疫组化染色,测定各组裸鼠瘤体Survivin蛋白表达量,并采用RT-PCR法检测裸鼠瘤体Survivin mRNA相对表达量。结果 与对照组比较,苦参碱50、75 mg/kg组裸鼠瘤体体积显著减小(P<0.01);苦参碱组裸鼠瘤体生长速度较对照组减慢,肝癌细胞分布较对照组稀疏,且剂量越大越明显。苦参碱50、75 mg/kg组仅有少量Survivin表达于细胞质。与对照组比较,苦参碱50、75 mg/kg组裸鼠Survivin蛋白表达量和Survivin mRNA相对表达量显著减小(P<0.01)。结论 苦参碱对人肝癌细胞HepG2荷瘤裸鼠具有抑瘤作用,有效剂量为50 mg/kg,其机制可能与下调Survivin表达、诱导肝癌细胞凋亡有关。

Objective To study the anti-tumor effect of matirine on human hepatocarcinoma cell line HepG2 implanted tumor in nude mice and explore its mechanism. Methods BALB/C nude mice were randomly divided into the control group and the matirine (25, 50, and 75 mg/kg) groups, and each group had 10 mice. Human hepatic cancer cells HepG2 were planted into BALB/C nude mice to establish the cancer models of HepG2. Mice in the control group were ip administered with normal saline 1 mL and those in the matirine groups were ip administered with 0.5, 1.0, and 1.5 mg/mL matirine solution 1 mL All mice were ig administered once daily, and treated for 35 d. Volume of implanted tumor and inhibitory rate were calculated. Pathological changes of the tumors with HE staining and SP staining were observed. Expression of Survivin was evaluated, and relative expression of Survivin mRNA of tumor in nude mice were determined by RT-PCR method. Results Compared with the control group, volumes of the implanted tumor in the matirine (50 and 75 mg/kg) groups were significantly decreased (P < 0.01). Compared with the control group, the growth speeds of tumor in the matirine groups were slower, liver cancer cell distributions were lager in dose-dependent manner, and small amounts of Survivin were expressed in the cytoplasm in the matirine (50 and 75 mg/kg) groups. Compared with the control group, expression of Survivin and relative expression of Survivin mRNA of tumor in the matirine (50 and 75 mg/kg) groups were significantly decreased (P < 0.01). Conclusion Matirine has anti-tumor effect on human hepatocarcinoma cell HepG2 tumor in nude mice with effective dose of 50 mg/kg, which may be attributed to down-regulate the expression of Survivin and inducing the apoptosis of hepatocellular carcinoma cells.

国家自然科学基金资助项目(30772859)