摘要
目的 采用血管内皮抑素转基因双歧杆菌口服制剂 (ETB 2 )对裸鼠结肠癌模型进行治疗 ,并探讨其抑瘤机制。方法 人结肠癌细胞LoVo接种于BALB/C裸鼠皮下建立动物模型 ,随机分为四组 :对照组 (6只 )以生理盐水灌胃、ETB 2A组 (9只 )、ETB 2B组 (9只 )、ETB 2C组 (9只 ) ,分别给予ETB 2 3.0、4 .5、6 .0 g·kg-1·d-1。接种后 2 4h灌胃给药 ,持续 2 1d ,第 2 8天处死动物 ,计算抑瘤率。观察病理变化 ,免疫组化检测微血管密度 (MVD)、增殖细胞核抗原 (PCNA)指数和血管内皮生长因子(VEGF)阳性率 ,RT PCR检测VEGFmRNA、TGF β1mRNA ,DNA原位末端标记 (TUNEL)检测凋亡率。结果 对照组抑瘤率为 0 ,ETB 2A、ETB 2B、ETB 2C分别为 2 3.7% ,5 9.2 % ,6 7.9% ,与对照组相比差异有显著性 (P <0 .0 5 ) ,ETB 2C组与ETB 2A组相比差异也有显著性 (P <0 .0 5 )。ETB 2A、ETB 2B、ETB 2C组MVD与对照组相比 ,差异有显著性 (P <0 .0 5 ) ,ETB 2B、ETB 2C组VEGF阳性率、VEGFmRNA、TGF β1mRNA与对照组相比差异有显著性 (P <0 .0 5 ) ;PCNA指数治疗组有降低趋势 ,但各组间比较差异无显著性 (P >0 .0 5 )。ETB 2A、ETB 2B、ETB 2C组凋亡率分别与对照组相比 ,差异有显著性 (P <0 .0 1)。结论 ETB 2可显著抑制裸鼠人结肠癌的生?
Objective The study was aimed to investigate the effects of endostatin transfected bifidobacterium oral preparation (ETB-2) on BALB/c nude mice colonic cancer and its mechanism. Methods The human colonic cancer cell line LoVo was implanted subcutaneously in BALB/C nude mice, then the mice were allocated into 4 groups: control group(n=6), ETB-2A(3.0 g·kg -1·d -1,n=9), ETB-2B(4.5 g·kg -1·d -1,n=9) and ETB-2C(6.0 g·kg -1·d -1,n=9). The ETB-2 was drenched after being implanted 24 hours, while saline water was given to the control groups. The drenching was given on for 21 days consecutively, then the mice were sacrificed on the 28th day and the rates of tumor inhibition were calculated. The pathologic changes were observed by conventional pathology; the microvessel density(MVD), proliferating cell nuclear antigen(PCNA) index and the positive rate of vascular endothelial growth(VEGF) were measured immunohistochemically; the apoptotic rate was analyzed with TDT mediated dUTP nick end labeling(TUNEL) technique; and the VEGF mRNA and TGF-β 1 mRNA were measured by RT-PCR. Results The tumor inhibition rates in ETB-2A(23.7%), ETB-2B(59.2%) and ETB-2C(67.9%) were significantly higher than that in control (0%,P< 0.05); the tumor inhibition rate in ETB-2C was significantly higher than that in ETB-2A(P< 0.05). MVD in ETB-2A, ETB-2B and ETB-2C were significantly decreased than that in control(P< 0.05). Although PCNA indices in experimental groups tended to decrease, but the difference of PCNA indices did not exist among control, ETB-2A, ETB-2B and ETB-2C. The positive rate of VEGF in ETB-2B and ETB-2C was significantly lower than that in control. As compared with control, VEGF mRNA in ETB-2B and ETB-2C was significantly decreased (P<0.05), while TGF-β 1 mRNA in ETB-2B and ETB-2C was significantly lower than that in control(P< 0.01,P<0.05). The apoptotic rate in ETB-2A, ETB-2B and ETB-2C was significantly higher than that in control(P< 0.01). Conclusions ETB-2 could significantly inhibit the growth of experimental human colon cancer in BALB/C nude mice and its action may be dose-dependent. The mechanism of action could be due to the antiangiogenic effect, increase of the apoptosis of tumor cells, inhibition of the expression of proangiogenic factor VEGF and TGF-β 1, and decrease of the proliferation of tumor cells.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2003年第6期355-358,共4页
Chinese Journal of Digestion
