SiRNA-Mediated RRM2 Gene Silencing Combined With Cisplatin In The Treatment Of Epithelial Ovarian Cancer In Vivo: An Experimental Study Of Nude Mice

Objective:We aimed to explore small interfering(si)RNA silencing of ribonucleotide reductase M2(RRM2)gene combined with cisplatin for the treatment of human ovarian cancer in nude mice models of subcutaneous transplantation tumors.Methods:After conventional cultivation of human ovarian cancer cell line SKOV3 in vitro,subcutaneous injections of subcutaneous ovarian cancer were administered to nude mice to create a transplantation tumor model.Twenty-four tumor-burdened rats were randomly divided into four groups(n=6): the control group,cisplatin group,siRNA group,and siRNA in combination with cisplatin group.Tumor volume was measured and tumor growth inhibition rate was calculated.RRM2 gene expression at mRNA level and protein level was detected by reverse transcription polymerase chain reaction and immunohistochemistry.Results:In the siRNA group,the tumor volume and tumor growth inhibition rate were 249.60±20.46 mm3 and 36.39%,respectively.The tumor growth inhibition rate and tumor volume were significantly different between the siRNA and control groups(p<0.05).In the cisplatin group,the tumor volume and tumor growth inhibition rate were 249.86±12.46 mm3 and 41.10%.The tumor growth inhibition rate and tumor volume were significantly different between the cisplatin and control groups(p<0.05).In the siRNA + cisplatin group,the tumor volume reduced to 180.84±16.25 mm3 and the tumor growth inhibition rate was increased to 64.33%,which were significantly different compared with the cisplatin group,siRNA group,and control group(p<0.01).Significant downregulation of RRM2 in the tumor tissues was detected by reverse transcription polymerase chain reaction and immunohistochemistry assay in siRNA group and siRNA + cisplatin group(p<0.05).Conclusion:siRNA alone or combined with cisplatin can effectively inhibit the growth of human ovarian cancer in nude mice models of subcutaneous transplantation tumors,which may be related to the silencing of RRM2 gene expression.RRM2 gene silencing may be a potential treatment regimen for ovarian cancer in future.