Effects Of Endostatin Transfected Oral Powder Preparation (ETB-2) On Experime-ntal Colon Cancer

Background/Aims To investigate the effects of endostatin transfected bifidobacterium oral preparation (ETB-2) on BALB/C nude mice colon cancer and its mechanism.Methods The human colon cancer line cell LoVo was implanted subcutaneously in BALB/C nude mice,then the mice were allocated into 4 groupsxontrol group(6 mice),ETB-2A(3g/kg/d,9 mice),ETB-2B(4.5g/kg/d. 9 mice),ETB-2C(6g/kg/d, 9 mice). The ETB-2 was given by drenching after being implanted 24 hours, while control groups were given saline water. The drenching were given on successive 21 days . then they were sacrificed on 28th day and the rate of tumor inhibition were calculated. Effects of ETB-2 on growth of LoVo in vitro were assayed by MTT method, 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(VEGP) were measured immunohistochemically and the apoptotic rate was analyzed with TDT mediated dUTP nick end labeling(TUNEL) technique, the VEGFmRNA> TGF-3-lmRNA were measured by RT-PCR.Results (1) The tumor inhibition rate in ETB-2A(23.67%), ETB-2B(59.25%), ETB-2C(67.90%) were significantly higher than in control (0%,P<0.05);the tumor inhibition rate in ETB-2C was significantly higher than in ETB-2A(P<0.05).(2) It was no effects of ETB-2 on growth of LoVo in vitro.(3) MVD in ETB-2A(17.30.14), ETB-2B( 13.22 .45), ETB-2C( 10.89 5.95) were significantly decreased than in control(23.83.91.P<0.05) ;MVD in ETB-2C was significantly decreased than in ETB-2A(P<0.05).AIthough PCNA index in experimental groups were tend to decreasing, the difference of PCNA Index in control(35.1711: 62), ETB-2A(34.7011.38), ETB-2B(31.89 .06), ETB-2C(29.44 8.08) were no found .The positive rate of VEGF in ETB-2B(31.33+ 12.07%), ETB-2C(25.4413.29%) were significantly lower than in control(55.50 2.66%), the positive rate of VEGF in ETB-2C was significantly lower than in ETB-2A(40.507.59%,P<0.05).When compared with controls (0.98 .23), VEGFmRNA in ETB-2B (0.54 .19), ETB-2C(0.45.23) were significantly decreased (PO.05),while TGF-P ImRNA in ETB-2B(0.70 .21), ETB-2C(0.34.8) were significantly lower than in contro(1. 13.52,P<0.01,PO.05), ETB-2C was also significantly lower than in ETB-2A(0.79.49,P<0.05). (5) The apoptotic rate in ETB-2A(40.60%.80%), ETB-2B(45.00%.02%), ETB-2C(49.67%.29%) were significantly higher than in control(3.0%.5%,P<0.01),the apoptotic rate in ETB-2C was also significantly higher than in ETB-2A(p<0.05).Conclusions ETB-2 could significantly restrain the growth of experimental human colon cancer in BALB/C nude mice and its action was of dose-dependent. The mechanism of action may bedue to its antiangiogenic effect, increasing apoptosis of tumor cells, inhibiting the expression proangiogenic factor VEGF.TGF- P l.also decreasing proliferation of tumor cells.