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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 inhibitory effect of angiogenesis inhibitor SU5416 on colon cancer growth and metastasis. Methods Human colon adenocarcinoma cell line SW1116 was implanted in nude mice in situ to establish a clinical model of colon cancer metastasis in nude mice. Intraperitoneal injection of physiological saline (control group), fluorouracil 5Fu group), SU5416 SU5416 group), and 5Fu combined with SU5416 group (combined group) were used for 7 weeks. Animals were sacrificed at 8 weeks after implantation. Tumor weight, tumor inhibition rate, tumor microvessel density (MVD), and apoptosis index (AI) of colon cancer cells were measured. Tumor cell, liver, other organ metastases, and ascites were observed. . Results The tumor weights in situ in the control group, 5Fu group, SU5416 group, and combination group were 138±0.42g, 0.71±0.26g, 0.25±0.13g, and 0.16±0.09g, respectively; the tumor inhibition rates were 0 and 48.6%, respectively. The MVD was 134±4.9, 11.7±4.2, 2.6±1.4, and 0.94±0.5, respectively; the AI was 3.59±2.46%, 6.81±5.97%, 12.83±4.56%, and 20.18±8.91%, respectively; The metastasis rates were 90.9%, 46.5%, 25.0%, 0; liver metastasis rates were 72.7%, 33.3%, 16.7%, 0. 5Fu, SU5416, and combination groups, respectively, compared with the control group, the colon between the groups. The inhibitory effects of cancer growth and metastasis were significantly different (P<0.05). Colon cancer growth and peritoneal and hepatic metastases were significantly inhibited (P<0.05). Conclusion SU5416 has a strong inhibitory effect on the growth and metastasis of colon cancer cells in vivo by inducing apoptosis of colon cancer cells through anti-angiogenesis, and it can act synergistically with traditional chemotherapy drugs.