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目的探讨血管内皮抑素转基因双歧杆菌口服制剂(ETB-2,E)联合5-Fu(F)、IFNα-2a(I)对裸鼠结肠癌的治疗效应,并探讨其作用机制。方法将人结肠癌细胞LoVo接种于BALB/c裸鼠皮下建立动物模型,随机分为6组,每组6只动物,除对照组用等量生理盐水灌胃外,余分别给予E、F、I、E+F、E+I等药物。6组均于接种后第22天处死动物,计算抑瘤率。观察病理变化,用免疫组化法检测微血管密度(MVD)、增殖细胞核抗原指数(PCNA指数)和血管内皮生长因子(VEGF)阳性率,用RT-PCR法检测VEGF mRNA、TGFβ-1mRNA,用DNA原位末端标记(TUNEL)法检测凋亡率。结果(1)对照组抑瘤率为0,E组、F组、I组、E+F组、E+I组抑瘤率分别为47.26%、60.69%、34.68%、71.23%、63.09%,E+F组、E+I组抑瘤率分别与E组、I组相比,差异有显著性(P<0.05)。(2)E+F组和E+I组MVD与对照组相比,差异有显著性(P<0.05);E+F组、E+I组VEGF阳性率分别与对照组、F组相比,差异有显著性(P<0.05);PCNA指数各治疗组有降低趋势,但各组间比较,差异无显著性(P>0.05)。(3)E+F组、E+I组VEGF mRNA、TGFβ-1mRNA较对照组、E组、F组、I组明显降低(P<0.05)。(4)E组、I组、E+F组、E+I组凋亡率与对照组相比,差异均有显著性(P<0.05)。(5)常规病理检查发现,E组血管明显减少,E+F组和E+I组则坏死较为严重,血管明显减少。结论ETB-2分别联合5-Fu、IFN-α2a可更有效地抑制裸鼠结肠癌的生长,具有协同作用。
Objective To investigate the therapeutic effect of endostatin-conjugated Bifidobacterium oral preparations (ETB-2, E) combined with 5-Fu (F) and IFNα-2a (I) on colon cancer in nude mice and to explore its mechanism. Methods Human colon cancer LoVo cells were inoculated subcutaneously into BALB / c nude mice to establish an animal model. The animals were randomly divided into 6 groups with 6 animals in each group. E, F, I, E + F, E + I and other drugs. 6 groups were sacrificed on the 22nd day after inoculation to calculate the tumor inhibition rate. Pathological changes were observed. MVD, PCNA index and VEGF positive rate were detected by immunohistochemistry. VEGF mRNA and TGFβ-1 mRNA were detected by RT-PCR. Apoptosis rate was detected by TUNEL method. Results The tumor inhibition rate of the control group was 0, the inhibition rate of the control group was 0, the inhibition rate of the group E, F, I, E + F and E + I were 47.26%, 60.69%, 34.68%, 71.23%, 63.09% The inhibition rates of E + F group and E + I group were significantly lower than those of E group and I group (P <0.05). (2) Compared with the control group, the MVD in E + F group and E + I group was significantly different (P <0.05). The positive rate of VEGF in E + F group and E + I group was significantly lower than that in control group and F group , The difference was significant (P <0.05); PCNA index decreased in each treatment group, but there was no significant difference between the groups (P> 0.05). (3) VEGF mRNA and TGFβ-1 mRNA in E + F group and E + I group were significantly lower than those in control group, E group, F group and I group (P <0.05). (4) The apoptosis rates of E group, I group, E + F group and E + I group were significantly different from those of the control group (P <0.05). (5) The results of routine pathological examination showed that the number of blood vessels in group E decreased significantly, while those in group E + F and group E + I were more severe and the blood vessels decreased significantly. Conclusions ETB-2 combined with 5-Fu and IFN-α2a can inhibit the growth of colon cancer in nude mice more effectively and has a synergistic effect.