山东大学学报 (医学版) ›› 2019, Vol. 57 ›› Issue (10): 74-79.doi: 10.6040/j.issn.1671-7554.0.2019.270
• 基础医学 • 上一篇
薛婷1,王黎明1,焦今文1,李勇1,郭爱莲1,赵涵2
XUE Ting1, WANG Liming1, JIAO Jinwen1, LI Yong1, GUO Ailian1, ZHAO Han2
摘要: 目的 探讨siRNA沉默核糖核苷酸还原酶M2(RRM2)基因联合顺铂治疗人卵巢癌裸鼠移植瘤的可行性。 方法 常规体外培养人卵巢癌细胞株SKOV3,采用皮下注射法建立卵巢癌裸鼠皮下移植瘤模型,将24只荷瘤鼠随机分为对照组、顺铂组、siRNA组、siRNA联合顺铂组,每组6只,分组给药。观察肿瘤生长情况,测瘤体积并计算肿瘤生长抑制率。采用RT-PCR和免疫组织化学方法分别检测肿瘤组织中RRM2 mRNA及蛋白表达。 结果 对照组、siRNA组、顺铂组和siRNA联合顺铂组平均肿瘤体积分别为(358.28±46.40)、(261.38±52.49)、(261.65±31.97)、(189.37±41.67)mm3,单药作用后肿瘤体积差异有统计学意义(FsiRNA-RRM2=22.399,PsiRNA-RRM2<0.001;F顺铂=22.254,P顺铂<0.001);两药间无交互作用(F=0.474,P=0.499)。对照组、siRNA组、顺铂组和siRNA联合顺铂组肿瘤生长抑制率分别为0、36.39%、41.10%、64.33%。siRNA-RRM2与顺铂单药各自均能降低RRM2 mRNA表达水平(FsiRNA-RRM2=9.37,PsiRNA-RRM2=0.006;F顺铂=11.90,P顺铂=0.003)和蛋白表达水平(FsiRNA-RRM2=8.71,PsiRNA-RRM2=0.008;F顺铂=13.01,P顺铂=0.002);两药间无交互作用(FRRM2 mRNA=3.93,PRRM2 mRNA=0.061;FRRM2蛋白=1.72,PRRM2蛋白=0.204)。 结论 单用siRNA或联用顺铂均可有效抑制人卵巢癌裸鼠皮下移植瘤瘤体的生长,可能与其沉默RRM2基因表达有关,特异性沉默RRM2或可成为卵巢癌治疗的一个新思路。
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