摘要
目的:研究藤黄对人结肠癌HCT116细胞建立的裸鼠外科原位移植瘤生长及转移的抑制作用.方法:通过外科原位移植能表达绿色荧光蛋白人结肠癌HCT116细胞的方法建立裸鼠结肠癌模型.40只模型裸鼠随机分为对照组(G1),5-氟尿嘧啶(5-fluorouracil,5-FU)组(G2),10、20 mg/kg藤黄组(G3、G4),每组10只.G1组采用生理盐水灌胃,1次/d;G2组用25 mg/kg的5-FU进行腹腔灌注,3次/wk;G3、G4组分别予相应剂量的藤黄提取物灌胃,1次/d.每天观察受试裸鼠的并发症及死亡情况,2次/wk在体外荧光影像系统下观察移植肿瘤大小并测量裸鼠体质量,实验终点处死所有受试裸鼠在开放荧光系统下观察肿瘤生长及转移情况,切除移植肿瘤进行称体质量.结果:药物干预后,20 mg/kg藤黄组各观察点的平均肿瘤体积(mm3)均小于对照组(d4:104.5±35.5 vs 164.1±66.1;d7:102.6±53.8vs 286.2±132.0;d11:137.6±70.5 vs 324.4±115.8;d14:207.2±101.7 vs 434.2±169.3;d21:229.8±99.8 vs 480.4±165.5),差异有统计学意义(P<0.05).实验终点20 mg/kg藤黄组的平均肿瘤质量轻于对照组(0.58 g±0.26 g vs 0.92 g±0.26 g),差异有统计学意义(P<0.05).20 mg/kg藤黄组与5-FU组之间比较,10 mg/kg藤黄组与对照组比较,无论是各观察点平均肿瘤体积还是实验终点肿瘤重量差异无统计学意义(P>0.05).实验终点开放体内荧光成像显示各组均出现了不同程度的胰腺及淋巴结转移,比较组间淋巴结及胰腺转移率的差异无统计学意义(P>0.05).实验过程中各组实验动物均未出现药物相关的不良反应,各组荷瘤裸鼠的平均体质量未出现明显波动.结论:藤黄在达到一定干预剂量(20 mg/kg)后能安全有效地抑制人结肠癌HCT116细胞裸鼠原位移植瘤的生长,可能具有潜在的临床抗结直肠癌作用.
AIM： To study the antitumor and anti-metastatic effects of gamboge in an orthotopic mouse mod- el developed with human colon cancer cell line HCT116.METHODS： A colon cancer model was devel- oped by surgical orthotopic implantation of green fluorescent protein （GFP）-expressing HCT 116 tumor in nude mice. Forty mice were equally randomized into four groups. Group 1 served as a negative control and received in- tragastric infusion of normal saline once daily. Group 2 received intraperitoneal injection of 5-fluorouracil at a dose of 25 mg/kg three times per week. Groups 3 and 4 received intragastric infusion of gamboge extract at a dose of 10 and 20 mg/kg, respectively, once daily. Each animal was checked for mortality and signs of morbid- ity every day. Primary tumor volume and me- tastasis for each animal were observed under a fluorescence imaging system twice a week and body weights were measured as well. At the end of the experiment, all mice were sacrificed and open fluorescent images of tumors and metastases expressing GFP were acquired, and the tumor was removed from each mouse and weighed. RESULTS： After initiation of different treatment regimens, the average tumor volume （ram3） was significantly smaller in the gamboge （20 mg/kg） group than the control group at each observation point （d4：104.5 ± 35.5 vs 164.1 ± 66.1; d7：102.6 ± 53.8 vs 286.2 ± 132.0; d11：137.6 ± 70.5 vs 324.4 ± 115.8; d14：207.2 ± 101.7 vs 434.2 ± 169.3; d21：229.8 ± 99.8 vs 480.4 ± 165.5; P 〈 0.05 for all）. At the end of the study, the average tumor weight was significantly smaller in the gamboge group （20 mg/kg） than in the control group （0.58 ± 0.26 vs 0.92 ± 0.26, P 〈 0.05）. There were no statistical dif- ferences between the gamboge （20 mg/kg） group and 5-fluorouracil group, as well as between the gamboge （10 mg/kg） group and control group, in term of average tumor volume and weight （P 〉 0.05 for all）. At the end of the experiment, open GFP imaging demonstrated that all groups presented metastasis of lymph nodes or the pan- creas, although there were no significant differ- ences between the four groups with regard to the metastasis rate （P 〉 0.05 for all）. No significant morbidity or weight loss was found in all tumor- bearing mice.CONCLUSION： Gamboge at a dose of 20 mg/kg was able to suppress HCT 116 tumor growth in an orthotopic mouse model of colon cancer safely and effectively, and may possess clinical therapeutic potential for colorectal cancer.
出处
《世界华人消化杂志》
CAS
北大核心
2014年第4期476-482,共7页
World Chinese Journal of Digestology
基金
江苏省自然科学基金资助项目
No.BK2008457
南京中医药大学校基础研究和重点培育基金资助项目
No.09XPY01~~
作者简介
通讯作者：谷云飞,教授，主任医师，210029，江办省南京市汉中路155号，南京中医药大学附属医院肛肠科guyunfeil27@126com电话：025-86617141
