The Anti-apoptosis Mechanism Of Sustained-release Fluorouracil And The MVD Level In Nude Mice With Human Colorectal Carcinoma

Objective To observe the MVD and survivin/caspase-3geneproteins expression level in nude mouse with colorectal carcinoma subcutaneoustransplanted by sustained-release fluorouracil implantation, and discussing themechanism of sustained-release fluorouracil. Methods To establish thecolorectal carcinoma subcutaneous transplanted model with LOVO cell usedBALB/c nude mice, and divided it into4groups randomly: the control grouprespectively the tail intravenous injected of PBS(A group); the tail intravenousinjected of5-FU group(B group);the intratumor injected of5-FU group(Cgroup);the implant of sustained-release fluorouracil group(D group). after thedrugs intervening, contrasting the tumor weight and tumor inhibiting rates, thetumor tissues were observed by HE staining and detected by IHC with thesurvivin/caspase-3and CD31(MVD). Results32nude mouse (total34nudemouse)is tumorigenesis successful after10days, the tumor formation rates is94%. The tumor volume of the four groups is as follows: A group(3672±809)mm~3、B group(2421±466)mm~3、C group(1663±693)mm~3、D group(951±500)mm~3,comparing the four groups (P<0.05,F=27.01). the tumor weight is as follows: A group (2.88±0.23) g、B group(2.31±0.20)g、C group(1.36±0.26)g、D group(0.51±0.10)g,comparing the four groups (P<0.05,F=27.01),the tumor inhibition rate D group(82.3%) is higher than B(19.8%)、Cgroup(52.8%).The HE stain result in400magnification is as follows：A groupthe tumor glandular tube is formed,having a small amount apoptosis and platynecrosis；B group the tumor atypia is obvious,the degree of malignancy ishigh,tumor glandular tube is not obvious,a little apoptosis and necrosis withbleeding can be seen. C group the tumor atypia is obvious, tumor glandulartube is not obvious, a little more apoptosis and necrosis with bleeding can beseen in local region.D group the tumor atypia is not obvious, tumor glandulartube is not obvious,the apoptosis is obvious and a little necrosis in local region.The HE stain in100magnification is as follows: A group the tumor invade fatand muscle;B group the tumor invade the fat and muscle in a little localregion;C group the tumor boundary is clear, the invasion is not seen; D groupthe tumor boundary is clear,the invasion of fat and muscle is not seen. Theexpress of survivin of four groups is as follows: A(51.50±20.09)%,B(36.63±13.61)%,C(31.63±11.81)%,D(17.00±8.26)%,the expression of survivin isgradual decline, comparing D with A、B、C,P<0.05；The express of caspase-3of four groups is as follows：A(6.75±1.67)%,B(21.13±3.68)%,C(48.5±6.61)%, D(72.88±.52)%, the expression of caspase-3is increasegradually,comparing D with A、B、C,P<0.05;calculating the MVD via CD31:A(51.88±5.06)%,B(43.13±8.18)%,C(39.50±4.54)%,D(26.50±4.53)%,comparing D with A、B、C,P<0.05；correlation analysis is used to analysissurvivin/caspase-3and surviving/MVD, along with the survivin decline, theexpression of caspase-3is going up (r=－0.653,p=0.000)；and with the survivin rising, the MVD is also go up(r=0.624, p=0.000). Conclusionsustained-release fluorouracil can develop the anticancer function in apoptosisby enhancing the expression of caspase-3and reducing the expression ofsurvivin,the decrease of survivin can influence angiogenesis and disturb thetumor blood supply,therefore, it suppression the tumor growth, It can kill thetumor efficiently, which promise new ideas in clinical practice.