南蛇藤乙酸乙酯提取物对荧光蛋白标记的HepG2细胞裸鼠移植瘤生长的抑制作用

目的 建立裸鼠原位人荧光蛋白肝癌移植瘤模型,采用活体荧光成像技术研究南蛇藤乙酸乙酯提取物对人肝癌生长的抑制作用.方法 BALB/c裸鼠肝脏接种荧光蛋白标记的人肝癌细胞(RFP-HepG2),建立肝癌动物模型并随机分为空白对照组(G1组)、奥沙利铂阳性对照组(G2组,25mg/kg)、南蛇藤小剂量治疗组(G3组,20mg/kg)、南蛇藤大剂量治疗组(G4组,40mg/kg)和南蛇藤预防治疗组(G5组,20mg/kg).治疗组自RFP-HepG2细胞接种第20天开始用药,每日给药1次,连续4周.奥沙利铂尾静脉注射给药,南蛇藤灌胃给药,G1组用等渗盐水替代.G5组自RFP-HepG2细胞接种第2天开始给药至治疗结束.活体荧光影像技术追踪肿瘤生长情况,测量移植瘤体积;治疗结束后切除肿瘤并称重.组间肿瘤体积和质量比较用t检验.结果 RFP-HepG2细胞接种第31天的影像扫描结果提示各组移植瘤体积出现差异,第45天达高峰,G1、G2、G3、G4、G5组的移植瘤体积分别为(803.1±512.3)mm3、(83.8±23.5)mm3、(852.7±502.6)mm3、(410.0±231.6)mm3、(120.5±60.1)mm3;G5组肿瘤体积较G1组明显减小(t=3.723,P＜0.01),与G2组间的差异无统计学意义(t=0.163,P＞0.05);G4组与G1组间的差异无统计学意义(t=2.156,P＞0.05),且均明显大于G2组(t=4.526,P＜0.05).G1、G2、G3、G4、G5组瘤体质量分别为(0.95±0.49)g、(0.36±0.09)g、(0.67±0.29)g、(0.48±0.15)g、(0.38±0.11)g;G2、G4和G5组瘤体质量明显小于G1组(t值分别为3.371、2.774和2.901,P值均＜0.05),G4组和G5组与G2组间差异无统计学意义(t值分别为1.735、0.259,P＞0.05),而G3组瘤体质量则明显高于G2组(t=2.684,P＜0.05).结论 大剂量南蛇藤对移植瘤具有明显的抑制作用,疗效稍低于奥沙利铂;预防用药组肿瘤的生长速度明显减弱,其作用与奥沙利铂相当.

Acetoacetate extract from celastrus orbiculatus thunb inhibits growth of RFP-xenografted human liver carcinoma

To investigate the inhibitory effect of acetoacetate extract from celastrus orbiculatus thumb (COT) on the growth of red fluorescent protein (RFP)-xenografted human hepatocellular carcinoma (HCC) in a nude mouse model. Human HCC HepG2 cells were transduced with RFP and inoculated into the liver of BALB/c nude mice. The tumor-bearing mice were randomly divided into five groups: control group (G1), oxaliplatin positive control group (G2; 25 mg/kg), COT low-dose group (G3; 20 mg/kg), COT high-dose group (G4; 40 mg/kg), and COT early treatment group (G5; 20 mg/kg). The early treatment group received oral COT from day 2 post-tumor implantation. All other mice were treated from day 20 post-tumor implantation. Growth of xenografted tumors was monitored weekly by in vivo real-time fluorescence imaging technology. At the end of the four-week treatment period, all mice were sacrificed and tumor tissues were collected and weighed. The two-sided t-test was used to evaluate intergroup differences in tumor volumes, final tumor weights, and final body weights. Mice treated with COT had significantly smaller xenografted tumors. On day 45 post-implantation, the mean tumor volumes (mm3) in the different groups were: G1, 803.1+/-512.3 ; G2, 83.8+/-23.5; G3, 852.7+/-502.6; G4, 410.0+/-231.6; and G5, 120.5+/-60.1. The mean tumor weights (g) were: G1, 0.95+/-0.49; G2, 0.36+/-0.09; G3, 0.67+/-0.29; G4, 0.48+/-0.15; and G5, 0.38+/-0.11. The differences in tumor weights from G2, G4 and G5 were significantly less than the weight in G1 (P less than 0.05); however, there was no significant differences between the tumor weights in G2, G4 and G5 (P more than 0.05). The tumor weight from the G2 group was significantly less than that of the G3 group (P less than 0.05). COT significantly inhibited the proliferation of human HCC in a nude mouse model. Early treatment with COT produced a more robust inhibitory effect, which was very similar to that achieved with oxaliplatin treatment.