Qin Xu, Zheng Shutao, Liu Tao, Liu Qing, Liang Meng, Li Xiuling, Sheyhidin Ilyar, Lu Xiaomei
Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, P.R., China; State Key Lab Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, P.R., China.
Mol Carcinog. 2014 Jul;53(7):526-36. doi: 10.1002/mc.22004. Epub 2013 Jan 28.
The c-Jun NH2 -terminal kinase (JNK) signal pathway has been implicated in the growth, cellular proliferation, and apoptosis in many kinds of carcinomas. However, the role of JNK in the development of esophageal squamous cell carcinomas (ESCCs) is unknown. To investigate the role of JNK in ESCC, in vitro, esophageal cancer cell line Eca109 was pretreated using SP600125, JNK specific inhibitor, then was subjected to MTT assay to examine cellular proliferation, flow cytometric analysis to detect apoptosis and cell cycle, and wound healing assay to evaluate cell migration. Meanwhile, the mRNA and protein expression of JNK in Eca109 cells pretreated with SP600125 were examined by real-time quantitative reverse transcription PCR (qRT-PCR) and Western blotting, respectively. In vivo, 12 paired of fresh ESCC and normal adjacent tissues (NAT) from Kazakh patients were used to validate the expression of JNK by qRT-PCR and Western blotting. Furthermore, to reconfirm the expression trend of activation JNK (p-JNK), enlarged 72 paired of Kazakh's ESCC and NAT were subjected to immunohistochemistry. Our results showed that the suppression of p-JNK could lead to apoptosis and reduce proliferation in Eca109 cells. However, there was an elevated expression of p-JNK protein in NAT compared with ESCC tissues, and there was significant difference between p-JNK expression and pathological differentiation (P < 0.05) in Kazakh populations. Together, all the data we obtained in the present study indicated that the p-JNK MAPK pathway was involved in pathogenesis of Kazakh's ESCC, and played a different roles in carcinogenesis and development of Kazakh's ESCC.
c-Jun氨基末端激酶（JNK）信号通路与多种癌症的生长、细胞增殖及凋亡有关。然而，JNK在食管鳞状细胞癌（ESCC）发生发展中的作用尚不清楚。为研究JNK在ESCC中的作用，在体外，先用JNK特异性抑制剂SP600125预处理食管癌细胞系Eca109，然后进行MTT试验检测细胞增殖，通过流式细胞术分析检测凋亡和细胞周期，采用伤口愈合试验评估细胞迁移。同时，分别通过实时定量逆转录PCR（qRT-PCR）和蛋白质免疫印迹法检测经SP600125预处理的Eca109细胞中JNK的mRNA和蛋白表达。在体内，采用12对哈萨克族患者的新鲜ESCC组织和癌旁正常组织（NAT），通过qRT-PCR和蛋白质免疫印迹法验证JNK的表达。此外，为再次确认活化型JNK（p-JNK）的表达趋势，对72对扩大样本的哈萨克族ESCC组织和NAT进行免疫组织化学检测。我们的结果表明，抑制p-JNK可导致Eca109细胞凋亡并减少增殖。然而，与ESCC组织相比，NAT中p-JNK蛋白表达升高，且哈萨克族人群中p-JNK表达与病理分化之间存在显著差异（P<0.05）。综上所述，我们在本研究中获得的所有数据表明，p-JNK MAPK信号通路参与哈萨克族ESCC的发病机制，并且在哈萨克族ESCC的发生和发展中发挥不同作用。
