SOCS3通过PYK2信号通路调控小细胞肺癌的HIF-1α表达及增殖潜能  

SOCS3 may regulate HIF-1α expression and cell proliferation by mediating PYK2 signaling pathways in the small cell lung cancer cell line

作　　者：万军[1] 车云[1] 康宁宁[1] 柴惠平[1] 

机构地区：[1]安徽医科大学第一附属医院普胸外科,合肥230022

出　　处：《癌症进展》2015年第1期74-78,共5页Oncology Progress

基　　金：国家自然科学基金(81302028);安徽省自然科学基金(1208085QH159)

摘　　要：目的通过观察缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)在小细胞肺癌中表达及增殖情况,探讨细胞因子信号途径抑制因子3(suppressor of cytokine signaling 3,SOCS3)通过脯氨酸丰富的酪氨酸激酶2(proline-rich tyrosine kinase 2,PYK2)信号通路对HIF-1α表达的影响。方法首先采用免疫荧光法检测转染Ad5-SOCS3后SOCS3的表达水平并绘制细胞生长曲线;其次建立实验用裸鼠移植瘤模型并分组,观察并记录移植瘤的生长速率、测量肿瘤体积、绘制肿瘤生长曲线图,并对瘤体称重;再次采用蛋白质印迹法检测HIF-1α、SOCS3、PYK2及Tyr402在裸鼠移植瘤中的表达情况。结果与Ad5转染组相比,Ad5-SOCS3转染组SOCS3蛋白的表达水平显著升高,小细胞肺癌细胞株和皮下移植瘤的增殖速率显著下降;而Ad5-SOCS3-HIF-1α共转染组的SOCS3蛋白表达水平、小细胞肺癌细胞株和皮下移植瘤的增殖速率均介于上述两组之间,且差异均有统计学意义(均P<0.05)。与未转染组相比,Ad5-SOCS3转染组和Ad5-SOCS3-HIF-1α共转染组小细胞肺癌HIF-1α表达水平、PYK2及其磷酸化活性形式Tyr402的表达水平均显著降低(均P<0.05);Ad5-SOCS3-HIF-1α共转染组的HIF-1α表达水平显著高于Ad5-SOCS3转染组(P<0.05),但两组PYK2和Tyr402的表达水平均无差异。结论 SOCS3可能通过调控HIF-1α表达水平来影响小细胞肺癌的增殖潜能。SOCS3可能通过PYK2信号通路调控HIF-1α的表达。Objective To explore the influence of SOCS3-mediated PYK2 signaling pathways on HIF-1α expres-sion and proliferation in small cell lung cancer （SCLC）. Method Immunofluorescence was applied to test the SOCS3 expression level after the transfection of Ad5-SOCS3 alone or Ad5-SOCS3-HIF-1α, and the cell growth curve was plotted. Then the transplantation tumor model in nude mice was established and grouped by non-transfec-tion group, Ad5 transfection group, Ad5-SOCS3 transfection group and Ad5-SOCS3-HIF-1α co-transfection group, of which the tumor growth rates, tumor size, tumor growth inhibition rates were observed, measured and calculated, re-spectively, and tumors were weighted. The expression levels of HIF-1α, SOCS3, PYK2 and Tyr402 were detected again by Western blot. Result Compared with Ad5 group, the SOCS3 protein expression increased significantly, and the proliferation of SCLC cell line and subcutaneous transplantation tumor dropped significantly in Ad5- SOCS3 group, while those values in Ad5-SOCS3-HIF-1α group were between that of Ad5 group and Ad5-SOCS3 group （all P〈0.05）. When compared with non- transfection group, the expression of HIF - 1α, PYK2 and Tyr402 in Ad5-SOCS3 group and Ad5-SOCS3-HIF-1α group were all significantly decreased （all P〈0.05）; but the expression of HIF - 1α in Ad5-SOCS3-HIF-1α group was higher than that of Ad5-SOCS3 group （P〈0.05）, while the expressions of PYK2 and Tyr402 in both groups were on the same level generally. Conclusion SOCS3 may influence the prolif-erative potential of SCLC by mediating HIF-1α expression, which might be regulated by SOCS3 through PYK2 sig-naling pathways.

关 键 词：小细胞肺癌 细胞因子信号途径抑制因子3 缺氧诱导因子-1α 脯氨酸丰富的酪氨酸激酶2 

分 类 号：R734.2[医药卫生—肿瘤]