Journal of Shandong University (Health Sciences) ›› 2019, Vol. 57 ›› Issue (10): 74-79.doi: 10.6040/j.issn.1671-7554.0.2019.270

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siRNA-mediated silencing of RRM2 in the treatment of epithelial ovarian cancer xenograft in nude mice

XUE Ting1, WANG Liming1, JIAO Jinwen1, LI Yong1, GUO Ailian1, ZHAO Han2   

  1. 1. Department of Gynecology;
    2. Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China
  • Published:2022-09-27

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Abstract: Objective To explore the feasibility of siRNA silencing of ribonucleotide reductase M2(RRM2)gene combined with cisplatin on the treatment of human ovarian cancer subcutaneous xenograft in nude mice. Methods After conventional cultivation of human ovarian cancer cell line SKOV3 in vitro, subcutaneous injections of ovarian cancer were administered to nude mice to create a xenograft model. Twenty-four tumor-burdened mice were randomly divided into the control group(n=6), cisplatin group (n=6), siRNA group (n=6), and siRNA+cisplatin group (n=6). Tumor volume was measured and tumor growth inhibition rate was calculated. RRM2 gene expressions at mRNA level and protein level were detected by RT-PCR and immunohistochemistry. Results After single drug treatment, the tumor volumes of control group, siRNA group, cisplatin group and siRNA+cisplatin group were(358.28±46.40),(261.38±52.49),(261.65±31.97)and(189.37±41.67)mm3, respectively, with a significant statistical difference (FsiRNA-RRM2= 山 东 大 学 学 报 (医 学 版)57卷10期 -薛婷,等.siRNA介导RRM2基因沉默治疗人卵巢癌裸鼠移植瘤 \=-22.399,PsiRNA-RRM2<0.001; Fcisplatin=22.254, Pcisplatin<0.001). There was no interaction effect between the two drugs (F=0.474,P=0.499). The tumor growth inhibition rates of the four groups were 0, 36.39%, 41.10% and 64.33%, respectively. The single drug(siRNA-RRM2 or cisplatin)treatment reduced the expression levles of RRM2 mRNA(FsiRNA-RRM2=9.37, PsiRNA-RRM2=0.006; Fcisplatin=11.90, Pcisplatin=0.003)and protein (FsiRNA-RRM2=8.71, PsiRNA-RRM2=0.008; Fcisplatin=13.01, Pcisplatin=0.002), with a significant statistical difference. There was no interaction effect between the two drugs (FRRM2 mRNA=3.93, PRRM2 mRNA=0.061; FRRM2 protein=1.72, PRRM2 protein=0.204). Conclusion siRNA alone or combined with cisplatin can effectively inhibit the growth of human ovarian cancer subcutaneous xenograft, 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.

Key words: Ribonucleotide reductase, siRNA/RNAi, Cisplatin, Ovarian cancer, Nude mice

CLC Number: 

  • R711.75
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