A study on the antitumor effect and mechanism of arsenic trioxide on lung adenocarcinoma
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Published on: March 3, 2023
Qixian Zheng1, Haiyu Liu1, Qianyuan Zhang2
1Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian, P.R. China.
Background:
Lung adenocarcinoma is a common malignancy that requires new treatments. Arsenic trioxide (ATO) exerts antitumor activity in various cancers; however, its mechanisms of action in lung adenocarcinoma remain unclear.
Methods:
The 24-h half-maximal inhibitory concentration (IC50) of ATO on human lung adenocarcinoma A549 cells was determined using the Cell Counting Kit-8 assay. Cells were treated with the IC50 concentration in the experimental group, and untreated cells served as the control group. A comparative assessment of cell proliferation, apoptosis, invasion, and migration was performed. Transcriptome sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to identify differentially expressed genes and enriched pathways. Candidate pathway proteins were validated by western blot analysis.
Results:
The 24-h IC50 of ATO was 99.12 μmol/L. The ATO-treated group exhibited reduced proliferation, increased apoptosis, and decreased invasion and migration ( P < 0.05) compared with that in the control group. Transcriptome analysis revealed 4,522 upregulated and 4,045 downregulated genes, with enrichment in the mammalian target of rapamycin (mTOR) signaling pathway, base excision repair (BER), and apoptosis pathways. At the protein level, total mTOR expression did not significantly change, 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 results indicate that ATO suppresses the malignant phenotype of A549 cells by inhibiting mTOR phosphorylation, downregulating key BER components, and activating the extrinsic and intrinsic apoptotic pathways, providing experimental evidence for further studies of ATO in lung adenocarcinoma therapy.
Insights
Arsenic trioxide (ATO) inhibits lung adenocarcinoma cell growth by reducing proliferation and invasion. It also triggers apoptosis by affecting key pathways like mTOR and base excision repair (BER).
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Lung adenocarcinoma is a prevalent cancer requiring novel therapeutic strategies.
- Arsenic trioxide (ATO) demonstrates antitumor effects across various cancers, but its precise mechanisms in lung adenocarcinoma are not fully understood.
Purpose of the Study:
- To investigate the effects of Arsenic Trioxide (ATO) on the malignant phenotype of human lung adenocarcinoma A549 cells.
- To elucidate the molecular mechanisms underlying ATO's action, focusing on cell proliferation, apoptosis, invasion, and migration.
Main Methods:
- Determined the half-maximal inhibitory concentration (IC50) of ATO using the Cell Counting Kit-8 assay.
- Performed transcriptome sequencing and bioinformatics analyses (GO, KEGG) to identify differentially expressed genes and pathways.
- Validated key protein expression changes using Western blot analysis.
Main Results:
- ATO treatment significantly reduced A549 cell proliferation, invasion, and migration while increasing apoptosis.
- Transcriptome analysis identified significant alterations in gene expression, with enrichment in mammalian target of rapamycin (mTOR) signaling, base excision repair (BER), and apoptosis pathways.
- Protein analysis revealed decreased levels of phosphorylated mTOR (p-mTOR), APE-1, Bcl-2, and Bcl-XL, and increased levels of cleaved caspase-8 and cleaved caspase-9.
Conclusions:
- ATO effectively suppresses the malignant phenotype of lung adenocarcinoma A549 cells.
- The observed effects are mediated by the inhibition of mTOR phosphorylation, downregulation of BER components, and activation of both extrinsic and intrinsic apoptotic pathways.
- These findings provide a basis for further research into ATO as a potential therapeutic agent for lung adenocarcinoma.
