β-Catenin signaling pathway regulates cisplatin resistance in lung adenocarcinoma cells by upregulating Bcl-xl.

The Wnt/β‑catenin signaling pathway has been reported to regulate cisplatin resistance in several types of cancer cell. The present study aimed to investigate the role and underlying mechanism of Wnt/β‑catenin signaling in cisplatin resistance of lung adenocarcinoma cells. Wild‑type and cisplatin‑resistant A549 human lung adenocarcinoma cells (A549/WT and A549/CDDP, respectively) were cultured in vitro and exposed to different cisplatin concentrations. Cells were incubated with 10 mM lithium chloride (LiCl) to activate β‑catenin signaling. Cell proliferation was determined using the MTS assay. Cell apoptosis was evaluated using Annexin V/propidium iodide double staining, followed by flow cytometry. β‑catenin was knocked down using small interfering RNA (siRNA). The intracellular distribution of β‑catenin was determined by immunocytochemistry, and the mRNA and protein expressions of target genes were examined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. β‑catenin and B‑cell lymphoma‑extra large (Bcl‑xl) were significantly upregulated in A549/CDDP cells compared with A549/WT cells (P<0.05). LiCl reduced the sensitivity of A549/WT cells to cisplatin (P<0.01); and upregulated, increased phosphorylation (P<0.05) and enhanced nuclear translocation of β‑catenin. LiCl also significantly elevated the mRNA and protein expression levels of Bcl‑xl (P<0.05). Notably, silencing of β‑catenin with siRNA decreased the mRNA and protein expression of Bcl‑xl, and sensitized A549/WT cells to cisplatin (P<0.01). The findings of the current study suggest that upregulation of β‑catenin signaling may contribute to cisplatin resistance in lung adenocarcinoma cells by upregulating Bcl‑xl. Therefore, molecular targeting of Wnt/β‑catenin signaling may sensitize lung cancer cells to cisplatin.