E Targeted Smac Combined DDP Reverse Drug-resistant Ocarian Cancer And Its Relationship With The Expression Of Survivin

Objective:To evaluate the effect of inhibiting growth of the tumor on nude mice models of SKOV3/DDP and the reverse action after given Smac and DDP,and observe the relationship between Smac and Survivin.Methods:1. To establis the subcutaneous xenotransplanted tumor model of SKOV3/DDP in nude mice, The tumor-bearing nude mice were randomly divided into five groups:NS group,DDP group,DDP+null plasmid group,Smac group,DDP+Smac group.2. The Smac plasmid and null plasmid were obtained by alkaline lysis method.3. Observe the effect of inhibiting the growth of subcutaneous xenotransplanted tumors and adverse effects to the nude mice after given Smac、 DDP、Smac+DDP.4. Observe the situation of metastasis of intra-abdorminal viscera and ascites formation.5. The Smac and Survivin expression in xenograft tumors were analyzed by immunohistochemical staining.Results:1. There is no significant difference in weight between five groups before treatment(P>0.05);After treatment,the weight increased in control group and Smac group,but the weight of DDP group、DDP+null plasmid group and DDP+Smac group were lighten,especially in DDP group(P<0.05),and no significant difference in weight among oter four groups befor and after treatment(P>0.05).2. The volume of xenograft tumors were no significant difference among five groups before treatment(F=0.25,P>0.05).Before the end of test, the xenograft tumors of control group was larger than oter four groups,the DDP+smac group was smallest and compared to the control group、DDP group、DDP+null plasmid group, there is significant difference in tumor volume(P<0.05),and there is significant difference in tumor volume between Smac group and control group(P<0.05),and no significant difference among other groups (P>0.05).3. There were no metastatic lesion and ascites formation inside the abdomen.4.There is obviously significant difference between Smac group,DDP+Smac group and control group、DDP group、DDP+null plasmid group in expression of Smac or Survivin(P<0.05);but no significant difference among other groups(P>0.05).5.There is obviously negative correlation between Smac and Survivin in control group、DDP group、DDP+null plasmid group and DDP+Smac group;but no obviously negative correlation in Smac group.Conclusions:1. Both Smac combined DDP and Smac can inhibit growth and proliferation to the xenograft tumors on mude mice models of SKOV3/DDP,but the combination group is better than the smac group. The role of inhibit growth and proliferation to the xenograft tumors is not obviously if only used DDP.2. The Smac is no obvious side effects to nude mice and the DDP+Smac group also found no obvious side effects.3.Smac is low expression and Survivin is high expression in drug-resistant ovarian cancer cells,Survivin can reduce expression after enhance the expression of Smac.4. Smac may reverse drug-resistance in ovarian cancer.5.Smac reduced the expression of survivin may be one of mechanisms to reverse drug-resistance in ovarian cancer.