c-Met抑制剂联合5氟尿嘧啶对人结肠癌SW620裸鼠移植瘤的抑制作用研究  

Effect of c-Met Inhibitor Combined with 5-fluorouracil on Transplanted Human Colon Cancer SW620 in Nude Mice

作　　者：崔凤[1] 曲迪[1] 于常华[1] 孙儒雅[1] 

机构地区：[1]哈尔滨医科大学附属第二医院,黑龙江哈尔滨150001

出　　处：《肿瘤学杂志》2016年第9期698-702,共5页Journal of Chinese Oncology

基　　金：黑龙江省青年科学基金项目(qc2012c073)

摘　　要：[目的]研究c-Met抑制剂PHA665752联合5氟尿嘧啶(5-fluorouracil,5-Fu)对人结肠癌细胞SW620生长的抑制作用及机制。[方法]选取48只4周龄的雄性裸鼠皮下接种人结肠癌细胞SW620,建立裸鼠移植瘤模型,随机分为对照组(2.5%二甲亚砜稀释液隔日用药)、5-Fu组(40mg/kg 5-Fu每隔3日给药)、PHA组(25mg/kg PHA665752隔日给药)、5-Fu+PHA组(40mg/kg 5-Fu每隔3日给药+25mg/kg PHA665752隔日给药)各12只。免疫组织化学SP法检测瘤体组织内的E-cadherin和Ki-67蛋白表达情况,TUNEL法检测细胞凋亡情况。[结果]治疗结束时,5-Fu组、PHA组、5-Fu+PHA组3组裸鼠的体重和瘤体体积均明显低于对照组(P<0.05),且5-Fu+PHA组裸鼠的瘤体体积显著低于5-Fu组、PHA组(P<0.05)。5-Fu组、PHA组、5-Fu+PHA组3组裸鼠的E-cadherin蛋白OD值显著高于对照组(P<0.05);5-Fu+PHA组裸鼠的E-cadherin蛋白OD值显著高于5-Fu组、PHA组(P<0.05);5-Fu组、PHA组、5-Fu+PHA组3组裸鼠的Ki-67蛋白OD值显著低于对照组(P<0.05);5-Fu+PHA组裸鼠的Ki-67蛋白OD值显著低于5-Fu组、PHA组(P<0.05);5-Fu组、PHA组、5-Fu+PHA组3组裸鼠的凋亡指数(apoptotic index,AI)显著高于对照组(P<0.05);5-Fu+PHA组裸鼠的AI值显著高于5-Fu组、PHA组(P<0.05)。[结论]c-Met抑制剂PHA665752联合5-Fu对人结肠癌细胞SW620生长的抑制有协同作用,其机制可能与上调E-cadherin、下调Ki-67表达有关。[Objective] To investigate the effect of c-Met inhibitor PHA665752 combined with 5-fluorouracil（5-Fu） on transplanted human colon cancer SW620 in nude mice. [Methods] Fortyeight 4-week male nude mice were inoculated subcutaneously with human colon cancer SW620 cells,and xenograft model in nude mice were established. The mice were randomly divided into 4groups with 12 in each group：control group（2.5% dimethylsulfoxide dilution was given every other day）,5-Fu group（40mg/kg 5-Fu was given every 3 days）,PHA group（25mg/kg PHA665752 was given every other day） and 5-Fu＋PHA group（40mg/kg 5-Fu every 3 days ＋ 25mg/kg PHA665752 every other day）. The expressions of E-cadherin and Ki-67 in cancer tissues were detected immunohistochemically,and the apoptosis of cancer cells was assayed by TUNNEL method. [Results] At the end of the treatment,the weight of nude mice and the volume of tumor in 5-Fu group,PHA group and 5-Fu＋PHA group were significantly lower than those in control group（P〈0.05）,and the volume of tumor in 5-Fu ＋PHA group was significantly lower than that in 5-Fu group and PHA group（P〈0.05）. The expression of E-cadherin in 5-Fu group,PHA group,5-Fu＋PHA group was significantly higher than that in control group（P〈0.05）,and the expression of Ecadherin in 5-Fu＋PHA group was significantly higher than that in 5-Fu group and PHA group（P〈0.05）. The expression of Ki-67 in 5-Fu＋PHA group was significantly lower than that in 5-Fu group and PHA group（P〈0.05）,and the expression of Ki-67 in 5-Fu group,PHA group,5-Fu＋PHA group was significantly lower than that in control group（P 0.05）. Apoptotic index（AI） in 5-Fu ＋PHA group was significantly higher than that in 5-Fu group and PHA group（P〈0.05）. [Conclusion] cMet inhibitor PHA 665752 and 5-Fu has synergistic effect on the inhibition of human colon cancer SW620 in vivo,which is associated with the up-regulation of E-cadherin expression and downregulation of Ki-67 expression.

关 键 词：c-Met抑制剂 氟尿嘧啶 结肠肿瘤 凋亡 

分 类 号：R735.3[医药卫生—肿瘤]