肌醇六磷酸和肌醇联合应用对结直肠癌肝转移血管生成因子的影响

EFFECTS OF INOSITOL HEXAPHOSPHATE COMBINED WITH INOSITOL ON ANGIOGENIC GROWTH FACTORS IN LIVER METASTASIS FROM COLORECTAL CANCER

目的通过建立小鼠肝转移模型探讨肌醇六磷酸(IP6)和肌醇(Ins)联合应用对肿瘤转移血管生成因子的影响。方法脾膜注射方法建立结直肠癌肝转移模型后,将48只BALB/c小鼠按体质量随机区组为IP6组、Ins组、IP6+Ins组、阴性对照组,每组12只。术后第2日,实验组小鼠给予剂量为80 mg/kg bw的IP6和Ins灌胃,合用组体积以1:1比例混合,对照组以等体积的生理盐水代替,每天1次。连续给药20d后处死小鼠,观察瘤重和肝转移抑制率;采用RT-PCR和免疫组织化学方法检测小鼠血管内皮生长因子(VEGF);碱性成纤维生长因子(b FGF);转化生长因子(TGF-β)m RNA和蛋白的表达。结果与对照组相比,IP6、Ins、IP6+Ins组小鼠的瘤重和肝转移抑制率都降低(P<0.05);VEGF、b FGF、TGF-β的m RNA和蛋白的表达水平降低(P<0.05),并且合用组的效果优于单独使用,P<0.05。结论 IP6和Ins联合应用通过阻滞肿瘤血管生成因子VEGF、b FGF、TGF-β的表达明显抑制肿瘤生长和肝转移的发生,并且合用的效果优于单独使用。

Objectve To investigate the effects of inositol hexaphosphate（IP6） and inositol（Ins） on angiogenic growth factors in tumor metastasis by establishing a model of liver metastasis in mice. Methods Forty-eight tumor bearing BALB/C mice injected with CT-26 cells in the spleen were randomly divided into four groups： IP6 group, Ins group, IP6＋Ins group and negative control group（n=12）. At the second day after operation, IP6 and Ins（80 mg/kg bw） was administered via the gastrointestinal tract to each experimental group. The volume of the combination group was 1：1, and the control group was treated with equal volume of saline, once a day. After 20 days, all the mice were sacrificed and the tumor inhibiting rates were obtained. The m RNA and protein levels of vascular endothelial growth factor（VEGF）,basic fibroblast growth factor（b FGF）,transforming growth factor beta（TGF-β） in liver tissue were assessed by RT-PCR and immunohistoc hemistry method respectively. Results Compared with the control group, the tumor inhibiting rates in the experimental groups were significantly reduced（P〈0 05）. The m RNA and protein levels of VEGF, b FGF and TGF-β were decreased, and the effect of the combination was more significant（P〈0.05）. Conclusion IP6 and Ins can significantly inhibit tumor growth and metastasis by inhibiting the expression of VEGF, b FGF, TGF-β, and the effect of combined application is better than alone.