The combined inhibitory effect of butaselen and decitabine against lung cancer cells.

The DNA methyltransferase inhibitor decitabine (DAC) is clinically approved for hematologic malignancies, but its efficacy in solid tumors, including lung cancer, remains limited. This study aimed to investigate the combined effects of the thioredoxin reductase (TrxR) inhibitor butaselen (BS/BS1801) and DAC on lung cancer cells in vitro. Human lung cancer cell lines (A549 and H1299) were used as an in vitro model. Cytotoxicity was assessed using the CCK‑8 assay. Combination index (CI) and dose‑reduction index (DRI) analyses were performed to evaluate the combined effects of BS and DAC. Cell proliferation was detected by colony formation assay, apoptosis by Annexin V/PI staining with flow cytometry, and migration by wound healing assay. Protein expression levels of DNMT1, Bcl‑2, Bax, HOXA9, p21, and E‑cadherin were determined by western blotting. The combination of BS and DAC resulted in enhanced inhibition of proliferation and migration, and increased induction of apoptosis compared with either agent alone in A549 and H1299 cells, under specific ratio and time conditions. The combined treatment was associated with downregulation of DNMT1, a reduced Bcl‑2/Bax ratio, and upregulation of HOXA9, p21, and E‑cadherin. These preclinical findings suggest that the combination of BS and DAC represents a mechanistically rationalized and promising therapeutic strategy for lung cancer that warrants further evaluation in in vivo models and early‑phase clinical trials.