【摘要】 目的:观察白细胞介素17A信号传导及转录蛋白3-血管内皮生长因子（IL-17A-Stat3-VEGF）信号通路激活对前列腺癌细胞迁移的作用,并探讨其相关机制。方法:选取73例前列腺手术标本,包括正常前列腺（NP）组织8例（癌旁正常组织）、良性前列腺增生组织（BPH） 30例和前列腺癌组织35例,免疫组织化学染色法检测NP、BPH和前列腺癌组织中IL-17A、白细胞介素17 RA （IL-17RA）、Stat3和VEGF的表达,并分析其与前列腺癌恶性程度的相关性;ELISA法检测健康对照组和前列腺癌组研究对象血清IL-17A、IL-6、VEGF和基质金属蛋白酶9 （MMP-9）水平。IL-17A重组蛋白处理前列腺癌细胞,细胞划痕实验和Transwell小室实验观察各组细胞迁移能力,Western blotting法检测各组PC3细胞中Stat3、p-Stat3和VEGF蛋白表达水平。结果:免疫组织化学染色检测,与NP组织比较,BPH组织中IL-17A和IL-17RA表达水平明显升高（P<0.05）,前列腺癌组织中IL-17A、IL-17RA、Stat3和VEGF表达水平明显升高（P<0.05）;与BPH组织比较,前列腺癌组织中IL-17A、IL-17RA、Stat3和VEGF表达水平明显升高（P<0.05）。ELISA法检测,前列腺癌患者血清IL-17A、IL-6和VEGF水平明显高于健康对照者（P<0.05）。在前列腺癌组织中,随着Gleason评分增加,IL-17A、IL-17RA、Stat3和VEGF表达水平明显升高（P<0.05）;IL-17A重组蛋白与PC3细胞共培养24 h,与空白对照组(0μg·L^-1IL-17A)比较,50和100μg·L^-1IL-17A组细胞迁移数明显增加（P<0.05）;50和100μg·L^-1IL-17A组PC3细胞中Stat3、p-Stat3和VEGF蛋白表达水平明显高于0和20μg·L^-1IL-17A组（P<0.05）。结论:IL-17A可以明显促进前列腺癌细胞的迁移,其机制可能与激活IL-17A-Stat3-VEGF信号通路有关联。更多还原

【Abstract】 Objective:To observe the effect of interleukin-17A-signal transducer and activator of transcription3-vascular endothelial growth factor（IL-17A-Stat3-VEGF）signaling pathway activation on the migration of prostatic cancer cells,and to explore the relative mechanism. Methods:A total of 73 prostatic samples including 8 cases of normal prostate（NP）tissue（adjacent normal tissue）,30 cases of benign prostatic hyperplasia（ BPH） tissue and35 cases of prostate cancer tissue. Immunohistochemical staining method was used to detect the expressions of IL-17A,IL-17 RA,Stat3 and VEGF in NP,BPH and prostate cancer tissues,and their correlations with the malignancy degrees of prostate cancer were analyzed. ELISA method was used to detect the serum levels of IL-17A,IL-6,VEGF and matrix metallopeptidase-9（MMP-9） of the subjects in healthy control group and prostate cancer group. The prostatic cancer cells were cultured with IL-17A recombinant protein in vitro,and scratching test and Transwell chamber experiment were used to observe the migration ability of the cells;Western blotting method was used to detect the expression levels of Stat3, p-Stat3 and VEGF in the PC3 cells in various groups. Results:The immunohistochemical staining results showed that the expression levels of IL-17A and IL-17 RA in BPH tissue were significantly increased compared with NP tissue（P<0. 05）;the expression levels of IL-17A,IL-17 RA,Stat3,and VEGF in prostate cancer tissue were higher than those in NP tissue（P<0. 05）. Compared with BPH tissue,the expression levels of IL-17A,IL-17 RA,Stat3,and VEGF in prostate cancer tissue were increased（P<0. 05）. The ELASA results showed that the serum levels of IL-17A,IL-6,and VEGF in the patients with prostate cancer were significantly higher than those in healthy controls（P<0. 05）. In the prostate cancer tissue,the expression levels of IL-17A,IL-17 RA,Stat3,and VEGF were significantly increased with the increasing of Gleason score（P<0. 05）.After the PC3 cells were co-cultured with IL-17A recombinant protein for 24 h,the number of migration cells in 50 and100 μg·L^-1 IL-17A groups was significantly increased compared with blank control group(0 μg·L^-1 IL-17A)（P<0. 05）;the expression levels of Stat3,p-Stat3,and VEGF in the PC3 cells in 50 and 100 μg·L^-1 IL-17A groups were significantly increased compared 0 and 20 μg·L^-1 IL-17A groups（P <0. 05）. Conclusion:IL-17A can obviously promote the migration of prostatic cancer cells,and its mechanism may be related with the activation of IL-17A-stat3-VEGF signaling pathway.更多还原