SU5416对结肠癌生长和转移抑制作用的实验研究

Inhibition of angiogenesis inhibit or SU5416 in growth and metastasis of human colon cancer implanted in nude mice

目的研究血管生成抑制因子SU5416对结肠癌生长和转移的抑制作用。方法采用人结肠腺癌细胞株SW1116完整组织块裸鼠原位种植,建立类似于临床的结肠癌转移裸鼠模型。分别自腹腔注射生理盐水(对照组)、氟尿嘧啶5Fu组)、SU5416制剂SU5416组)、5Fu与SU5416联合应用(联用组),共用7周。种植后第8周处死动物,测量原位肿瘤瘤重、抑瘤率、肿瘤微血管密度(MVD)、结肠癌细胞凋亡指数(AI),观察肿瘤细胞腹膜、肝、其他脏器转移及腹水情况。结果对照组、5Fu组、SU5416组、联用组的原位肿瘤瘤重分别为138±0.42g、0.71±0.26g、0.25±0.13g、0.16±0.09g;抑瘤率分别为0、48.6%、81.9%、88.4%;MVD分别为134±4.9、11.7±4.2、2.6±1.4、0.94±0.5;AI分别为3.59±2.46%、6.81±5.97%、12.83±4.56%、20.18±8.91%;腹膜转移率分别为90.9%、46.5%、25.0%、0;肝转移率分别为72.7%、33.3%、16.7%、0。5Fu组、SU5416组、联用组分别与对照组相比,组间结肠癌生长和转移的抑制作用差异有显著性意义(P<0.05)。结肠癌的生长和腹膜、肝转移受到明显抑制(P<0.05)。结论SU5416通过抗肿瘤血管生成诱导结肠癌细胞凋亡对体内结肠癌生长和转移具有强烈的抑制作用,且与传统化疗药物联用可起协同作用。

Objective To study the effects of angiogenesis inhibitor SU5416on the growth and metastasis of colon cancer in vivo.Methods Metastatic model simulating human c olon cancer was established by orthotopic implanta tion of histologically intact human tumor tissue into colon wall of nude mice.Mice were randomly divided int o 4groups according to the different agents injected into the peritoneal cavity:control group(saline solution),5-Fu group(fluorouracil 30mg ·kg -1 ·d -1 i.p.),SU5416group(SU541616mg ·kg -1 ·d -1 i.p.),combined treatment group(both 5-Fu and SU5416).Eight weeks after implantation,the tumor weight,inhibition rates ,intratumoral microv essel density(MVD),apoptotic index(AI )and the presence of metastasis were e valuated respectively after the mic e were sacrificed.Results Compared with control group,the orthotopically implanted tumors were s ignificantly reduced in weight in mice treated with 5-Fu,SU5416and co mbined treatment with correspondin g inhibition rates 48.6%,81.9%and 88.4%respectively .MVD also decreased significantly in the tr eated mice[(13.4±4.9)versus(11.7±4.2),(2.6±1.4)and(0.94±0.5)].AI increased significantly in the t reated mice[(3.59±2.46)%versus(6.81±5.97)%,(12.83±4.56)%and(20.18±8.91)%].Liver metastasis was also inhibited and the incidence s decreased significantly in 5-Fu group,SU5416group and combined group than that in control group(72.7%versus 33.3%,16.7%and 0).The incidences of peritoneal metastasis also decreased signific antly in 5-Fu group,SU5416group and combined group than that in control group(90.9%versus 46.5%,25.0%and 0)(P<0.05).The growth and metastasis of human c olon cancer implanted in nude mice were significantly inhibited in SU5416gro up and combined group than that in5-Fu group.MVD decreased and AI increased significantly as well(P<0.05).Conclusions SU5416can induce apoptosis of colon cancer by i nhibiting tumor angiogenesis and has strong inhibitory effect both on tumor growth and metastasis of human colon cancer implanted in nude mice.Combination of SU5416with cytotoxic agents could be more effec tive.