Lung cancer remains one of the most common
cancer-associated mortalities worldwide, and
platinum-based doublet
chemotherapies are recommended as the first‑line treatment for advanced non‑small cell
lung cancer (NSCLC). However, the frequent development of multidrug resistance, to
cisplatin regimens in particular, is a major cause of
chemotherapy failure in patients with aggressive NSCLC. Wnt/β‑catenin signaling and sex‑determining region Y box 2 (Sox2) have been implicated in the development and progression and resistance to
epidermal growth factor receptor‑targeting
therapy in
lung cancer. The present study aimed to explore the effects of Wnt/β‑catenin and Sox2 signaling on the chemoresistance of cisplatin‑resistant
lung cancer cells by assessing the effects of Sox2 on Wnt/β‑catenin signaling activity, cell migration, invasion and clonogenicity, and susceptibility to
cisplatin in
lung adenocarcinoma A549 cells and
cisplatin-resistant A549/DDP cells. The results demonstrated that an enforced expression of Sox2 led to inhibition of Wnt/β-
catenin signaling activity, potentially by upregulating
glycogen synthase kinase 3 β in A549 and A549/DDP cells. An overexpression of Sox2 promoted cell migration and invasion, in addition to enhancing the clonogenic capacity in A549 cells. Notably, knockdown Sox2 using
short hairpin RNA led to an enhanced susceptibility of A549 and A549/DDP cells to
cisplatin, along with increased cell apoptosis. The present study thus suggests that Sox2 may be an important regulator in development of chemoresistance of
lung cancer cells and may be a novel therapeutic target for treatment chemoresistant
lung cancer.