AG490 Regulates The Expression Of Survivin And STAT3 Signal Transduction Pathway Of Human Cervical Cancer Xenografts In Nude Mice

Objective:To investigate the effects of AG490 on human cervical cancer xenografts in nude mice growth and apoptosis,as well as the relationship between the expression of Survivin and STAT3 signal transduction pathway.Methods:Establish the model of human cervical cancer xenografts in nude mice, nude mice were subcutaneously implanted with human cervical cancer cancer Hale cell on the right side of nude mice's back,and divided into 4 groups after 30 days:control group,DDP group,AG490 group,and AG490 with DDP group, AG490(8mg/kg),DDP(5mg/kg)and AG490 with DDP group(8mg/kg+5mg/kg)were administrated i.p./3d,a total of 4 times injection in nude mice were killed the day after drug withdrawal.The tumor volumes and changes in body weight were measured respectively during the therapy time.The tumor growth inhibiting rates of each group were calculated,the curves of tumor growth were drew.The expression of p-STAT3 and Survivin by immunohistochemistry in the xenografts.Flow cytometry was applied to analyze the cell apoptosis.Results:(1)Significant differences in average tumor volumes and tumor growth inhibition rates were found between the treatment group and the control group(P＜0.05).The tumor volumes in combination group were significantly less than those of other groups(P＜0.05).Compared with DDP group and AG490 group,the growth inhibiting rates of tumor in combination group were significantly higher. AG490 group compared with the control group had no significant changes in body weight difference(P=0.19).(2) DDP group,AG490 group and the combined group apoptosis rate of 52.1%,39.5%,66.7%,the control group do not form a clear-apoptosis,Each group with the control group compared to 10.2±2.4%were significantly different(P＜0.05).(3) tumor necrosis rate of the average:the control group 21.8±9.0%,AG490 group 39.4±11.3%,DDP group 40.8±7.3%,DDP+ AG490 group 61.9±9.6%,Each group with the control group compared were significantly different(P＜0.05),Significant differences in DDP+AG490 group Compared with DDP group and AG490 group(P＜0.05).(4)SP The positive rate of each group were:P-STAT3:the control group 92.5%;DDP group 64%;AG490 group 55%;DDP+AG490 group 40.9%;Survivin:control group,90.4%;DDP group 53.9%; AG490 group 52.1%;DDP+AG490 group 36.8 percent;in the control group have a high expression about P-STAT3 and Survivin,diminishing the expression of P-STAT3,Survivin after the therapy.Conclusion:1.AG490 with DDP alone and in combination can inhibit tumor growth of cervical cancer and promote cancer cell apoptosis,while cancer cells P-STAT3,Survivin expression and activity decreased significantly.2.Combined use of AG490+DDP showed a synergic effect.3.AG490 can enhance DDP the drug sensitivity and reduce the side effects of drugs.AG490 and DDP suppressed the growth of cervical cancer cell lines,induced significant.apoptosis in cervical cancer cell lines.;diminishing the expression of P-STAT3,Survivin,AG490 and DDP may provide a new therapeutic approach for treating cervical cancer.