崔 凤,曲 迪,于常华.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[J].肿瘤学杂志,2016,22(9):698-702. |
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 |
投稿时间:2015-12-04 |
DOI:10.11735/j.issn.1671-170X.2016.09.B002 |
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中文关键词: c-Met抑制剂 氟尿嘧啶 结肠肿瘤 凋亡 |
英文关键词:c-Met inhibitor fluorouracil colon neoplasms apoptosis |
基金项目:黑龙江省青年科学基金项目(qc2012c073) |
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中文摘要: |
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。 |
英文摘要: |
Abstract:[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] Forty-eight 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 4 groups 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 E-cadherin 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] c-Met 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 down-regulation of Ki-67 expression. |
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