下调Socs3表达增加肾癌细胞对干扰素α敏感性的实验研究  

Down-regulating Socs3 expression increases the sensitivity of renal carcinoma cells to interferon alpha

作　　者：穆志远 胡杰[1] 李永章 庞聪[1] MU Zhiyuan;HU Jie;LI Yongzhang;PANG Cong(Department of Urology,Langfang People′s Hospital,Langfang 065000,China)

机构地区：[1]廊坊市人民医院泌尿外科,河北廊坊065000 [2]河北省中医院泌尿外科,050011

出　　处：《临床肿瘤学杂志》2024年第3期220-223,共4页Chinese Clinical Oncology

摘　　要：目的探索抑制细胞因子信号转导SOCS蛋白是否可以降低肾细胞癌的IFN抗性及可能机制。方法培养人肾癌ACHN细胞并转染SOCS3 siRNA,采用实时荧光定量PCR(qPCR)和Western blotting检测SOCS家族的mRNA、蛋白表达;采用MTT法检测细胞增殖活性;建立小鼠肾癌肺转移模型,记录小鼠的生存情况。结果与对照组比较,IFN-α处理组SOCS3 mRNA表达显著增加(4.96±0.21 vs.103.22±0.24,P<0.001)。MTT法结果显示,与阴性对照组(转染NC-siRNA)比较,5.0、12.5、25.0、50 nmol/L SOCS3 siRNA可显著降低IFN-α处理组ACHN细胞增殖率(P<0.05)。Western blotting结果显示,与阴性对照组比较,SOCS3 siRNA组中p-STAT1及p-STAT3表达明显升高(p-STAT1:1.87±0.07 vs.1.02±0.01,P<0.001;p-STAT3:1.35±0.24 vs.1.12±0.03,P<0.05)。敲低SOCS3表达可增强IFN-α治疗肾癌肺转移小鼠的生存。结论下调SOCS3表达增强了STAT1激活和IFN-α的体外和体内抗肿瘤活性。基于SOCS3在介导对IFN-α免疫疗法的耐药性中发挥的作用,使用靶向SOCS3的siRNA和IFN-α的联合疗法可能是治疗肾癌及肾癌肺转移癌的有吸引力的候选药物。Objective To explore whether inhibition of cytokine signal transduction SOCS protein can reduce IFN resistance in renal cell carcinoma and its possible mechanism.Methods Human renal carcinoma ACHN cells were cultured and transfected with SOCS3 siRNA.Real-time quantitative fluorescent PCR(qPCR)and Western blotting were used to detect the mRNA and protein expression of SOCS family.Cell proliferation activity was detected by MTT assay.The lung metastasis model of mouse kidney cancer was established and the survival of mice was recorded.Results Compared with the control group,SOCS3 mRNA expression in IFN-αtreated group was significantly increased(4.96±0.21 vs.103.22±0.24,P<0.001).MTT assay showed that compared with the negative control group(transfected with NC-siRNA),5.0,12.5,25.0,50 nmol/L SOCS3 siRNA significantly decreased the proliferation rate of ACHN cells in IFN-αtreated group(P<0.05).Western blotting result showed that compared with the negative control group,the expression of p-STAT1 and p-STAT3 in SOCS3 siRNA group was significantly increased(p-STAT1:1.87±0.07 vs.1.02±0.01,P<0.001;p-STAT3:1.35±0.24 vs.1.12±0.03,P<0.05).Knocking down SOCS3 expression enhances survival of IFN-αtreated mice with renal carcinoma and lung metastasis.Conclusion Down-regulating SOCS3 expression enhances STAT1 activation and IFN-αantitumor activity in vitro and in vivo.Based on SOCS3′s role in mediating resistance to IFN-αimmunotherapy,combination therapy using SocS3-targeted siRNA and IFN-αmay be an attractive candidate for the treatment of kidney cancer and renal lung metastatic cancer.

关 键 词：肾癌 IFN-Α SOCS3 

分 类 号：R737.11[医药卫生—肿瘤]