The Experiment On The Inhibitory Effects Of MK886 In Combination With 5-FU On The Growth Of Human Colon Carcinoma In Nude Mice Implanted With HT-29 Cell

[Objective]: To inverstigate the effects and mechanisms of MK886 combined with 5-FU for the growth of human colon carcinoma in nude mice implanted with HT-29 cell[Methods]: In this experiment, 20 BALB/c-nu/nu mice, which had been inoculated human colon carcinoma cell line HT-29 subcutaneously, were divided into four groups at random and received treatments subcutaneously every other day. The four groups were: group A(control): DMSO; group B:MK886; group C: 5-FU; D: MK886+5-FU . We measured the volume of transplanted tumors every 4 days.Ater 28 days, the mice were killed and the volume and weight of tumors were calculated according to the formula:V=ab2/2(mm3) .5-LOX, microvessel density (MVD) and VEGF expressed on tumors were detected by immunohistochemisty. The TUNNEL assay was used to examine the apoptosis alteration of tumor cell in nude mice .[Results]: In DMSO , MK886,5-FU and combined group the data showed that weights of tumor(g) were 1.986+0.024, 0.952+0.051, 0.736+0.040,and 0.458+0.085 respectively;the tumor inhibition rate(%) was 22.29,69.52,86.48,0,respectively; the tumor's volume (mm3)was 1687.0+212.7,762.4+67.6,587.4+65.5,402.2+80.5 respectively. The tumor growth of every therapeutic groups was significant different from the control at 14 days.The tumors of combined group were efficiently smaller in volume and lower in weight than those in control group from 7 days (p<0.05) and than those in MK886 or 5-FU group.The group 5-FU had higher inhibition rate of tumor than MK886 treatment group,but there were not statistics significant. Compared with the control and 5-FU groups, the protein of 5-LOX , MVD and VEFG expressed lower than in MK886 treatment group and combination group tumor cells(p<0.01). The apoptosis index(AI) of tumor cells with MK886 treatment and combined treatment was higher than that of control group(p<0.01).The expression of 5-LOX, VEGF and amount of MVD in tumor tissues was not significant between the 5-FU and control group(p>0.05). The apoptosis index of tumor with 5-FU treatment was marked higher than that of control group(p<0.01).[Conclusions]: MK886 and 5-FU can inhibit the growth of colon carcinoma . The mechanisms of inhibiting implanted tumor growth and inducing cell apoptosis with MK886 treatment may be associated with down regulation of 5-LOX and VEGF expression. 5-LOX inhibits the angiogenesis of tumor and the combinating therapy of 5-LOX with 5-FU shows more marked inhibition on the growth of colon carcinoma.