Doublecortin-like kinase 1 (DCLK1) is involved in tumorigenesis, tumor growth and metastasis, and epithelial-to-mesenchymal transition in many digestive tract tumors. It is reportedly highly expressed in Barrett’s esophagus and esophageal adenocarcinoma, but its effects on the occurrence and progression of esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, real-time PCR and western blot analysis confirmed significant upregulation of DCLK1 expression in human ESCC tissues and cell lines. CCK-8 assay showed that transfection with siRNA against DCLK1 (si-DCLK1) markedly inhibited cell proliferation and colony formation in the ESCC cell lines Eca109 and TE1. Transwell assay revealed that si-DCLK1 transfection inhibited the migratory and invasive capacities of Eca109 and TE1 cells. Moreover, si-DCLK1 increased the chemosensitivity of these cells to cisplatin, as indicated by inhibited cell viability and colony formation, and increased ROS and apoptosis in cisplatin-treated cells. Western blot assay revealed that expression of nuclear β-catenin and c-Myc was significantly increased in ESCC tissues and that si-DCLK1 markedly downregulated nuclear β-catenin and c-Myc in Eca109 cells. Treatment with lithium chloride, an activator of β-catenin signaling, partially abolished the si-DCLK1-induced inhibition of proliferation, migration, invasion, and chemoresistance of ESCC cells. These findings suggest that knockdown of DCLK1 may inhibit the progression of ESCC by regulating proliferation, migration, invasion, and chemosensitivity via suppressing the β-catenin/c-Myc pathway, supporting a promising therapeutic target against ESCC.

在许多消化道肿瘤中，Doublecortin样激酶1（DCLK1）参与肿瘤发生，肿瘤生长和转移以及上皮到间质转化。据报道，它在巴雷特食管和食管腺癌中高表达，但其对食管鳞状细胞癌（ESCC）发生和发展的影响尚不清楚。在这项研究中，实时PCR和蛋白质印迹分析证实了人类ESCC组织和细胞系中DCLK1表达的显着上调。CCK-8分析表明，针对DCLK1（si-DCLK1）的siRNA转染显着抑制了ESCC细胞株Eca109和TE1中的细胞增殖和集落形成。Transwell分析表明，si-DCLK1转染抑制Eca109和TE1细胞的迁移和侵袭能力。此外，si-DCLK1增加了这些细胞对顺铂的化学敏感性，如抑制的细胞活力和集落形成所表明的那样，并增加了顺铂处理过的细胞中的ROS和凋亡。Western blot分析表明，ESCC组织中核β-catenin和c-Myc的表达显着增加，而si-DCLK1显着下调了Eca109细胞中核β-catenin和c-Myc的表达。用β-catenin信号激活剂氯化锂处理，部分废除了si-DCLK1诱导的ESCC细胞增殖，迁移，侵袭和化学抗性的抑制作用。这些发现表明，通过抑制β-catenin/ c-Myc途径来调节增殖，迁移，侵袭和化学敏感性，DCLK1的敲低可能会抑制ESCC的进展，从而有望成为针对ESCC的治疗靶标。