胰岛素样生长因子结合蛋白-6在舒尼替尼治疗肾透明细胞癌中的作用

Role of IGFBP-6 in the Treatment of Clear Cell Renal Cell Carcinoma by Sunitinib

目的观察胰岛素样生长因子结合蛋白-6(IGFBP-6)在舒尼替尼治疗肾透明细胞癌(ccRCC)中的作用。方法实时定量聚合酶链反应(RT-PCR)及蛋白质印迹法(Western blotting法)比较人肾皮质近曲小管上皮细胞HK-2与人ccRCC细胞株786-O中mRNA及蛋白表达差异;将舒尼替尼作用于786-O细胞系,观察舒尼替尼对IGFBP-6 mRNA及蛋白表达的影响;小干扰RNA(siRNA)抑制IGFBP-6基因表达,观察该过程对786-O细胞增殖的影响。结果HK-2细胞系IGFBP-6 mRNA和蛋白表达较786-O细胞系分别下降67.1%和61.8%,差异有统计学意义(P<0.01);上述两个细胞系比较,50μmol·L^(-1)舒尼替尼作用于786-O细胞系24 h,IGFBP-6基因mRNA及蛋白表达均增加,差异有统计学意义(P<0.01);siRNA抑制IGFBP-6基因表达能逆转舒尼替尼对786-O细胞增殖的影响,差异有统计学意义(P<0.01)。结论IGFBP-6蛋白与ccRCC发生、发展相关,IGFBP-6蛋白可能是舒尼替尼治疗ccRCC的一个药物靶点。

Objective To investigate the role of insulin-like growth factor binding protein-6(IGFBP-6)protein in the treatment of clear cell renal cell carcinoma(ccRCC)by sunitinib.Methods Real-time quantitative polymerase chain reaction(RT-PCR)and Western blotting were used to compare human normal renal tubular epithelial cell lines(HK-2)differences in mRNA and protein expression between human renal clear cell carcinoma cell line(786-O).The 786-O cell line were treaded with sunitinib to observe the effect of sunitinib on IGFBP-6 mRNA and protein expression;Inhibited IGFBP-6 gene by small interfering RNA(siRNA),and the effect of this process on the proliferation of 786-O cells was observed.Results The mRNA and protein expression of IGFBP-6 in the HK-2 cell line decreased by 67.1%and 61.8%compared to the 786-O cell line,respectively,and the difference was statistically significant(P<0.01).The expression of IGFBP-6 gene mRNA and protein on 786-O were both increased after treated with sunitinib(50μmol·L^(-1))for 24 hours,and the difference was statistically significant(P<0.01).Inhibited the IGFBP-6 gene expression by siRNA could reverse sunitinib against the effect of 786-O cell proliferation(P<0.01).Conclusion IGFBP-6 is related to the occurrence and development of ccRCC.At the same time,it may be a drug target for during sunitinib treatment for ccRCC.