A study on the anti-tumor effect and mechanism of arsenic trioxide on lung adenocarcinoma

Background Lung adenocarcinoma is a common malignancy that urgently requires novel pharmacological interventions. Arsenic trioxide (ATO) has demonstrated antitumor activity in various cancers, but its mechanisms of action in lung adenocarcinoma cells remain unclear. Methods The 24-hour half-maximal inhibitory concentration (IC50) of ATO on human lung adenocarcinoma A549 cells was determined using the Cell Counting Kit-8 (CCK-8). Cells treated at this concentration comprised the experimental group, and untreated cells served as the control group. Comparative assessments of cell proliferation, apoptosis, invasion, and migration were performed. Transcriptome sequencing followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses was conducted to identify differentially expressed genes and enriched pathways. Key pathway proteins were validated by Western blot. Results The 24-hour IC50 of ATO was 99.12 µmol/L. Compared with the control group, the ATO-treated group showed inhibited proliferation, increased apoptosis, and reduced invasion and migration (P < 0.05). Transcriptome analysis identified 4,522 upregulated and 4,045 downregulated genes, with enrichment in the mTOR signaling pathway, base excision repair (BER), and apoptosis pathways. At the protein level, total mTOR expression did not change significantly, whereas phosphorylated mTOR (p-mTOR), APE-1, Bcl-2, and Bcl-XL were downregulated, and cleaved caspase-8 and cleaved caspase-9 were upregulated (P < 0.05). Discussion These findings indicate that ATO may suppress the malignant phenotypes of A549 cells by inhibiting mTOR phosphorylation, downregulating key BER components, and activating both extrinsic and intrinsic apoptotic pathways, providing experimental evidence for further investigation of ATO in lung adenocarcinoma therapy.