Down-regulating Socs3 expression increases the sensitivity of renal carcinoma cells to interferon alpha
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-α treated 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-α treated 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-α treated mice with renal carcinoma and lung metastasis.Conclusion Down-regulating SOCS3 expression enhances STAT1 activation and IFN-α antitumor activity in vitro and in vivo.Based on SOCS3's role in mediating resistance to IFN-α immunotherapy,combination therapy using SocS3-targeted siRNA and IFN-α may be an attractive candidate for the treatment of kidney cancer and renal lung metastatic cancer.
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