Tumour growth‑suppressive effect of arsenic trioxide in squamous cell lung carcinoma

Leung,Leanne Lee; Lam,Sze‑Kwan; Li,Yuan‑Yuan; Ho,James Chung‑Man

doi:10.3892/ol.2017.6646

Tumour growth‑suppressive effect of arsenic trioxide in squamous cell lung carcinoma

Authors:
- Leanne Lee Leung
- Sze‑Kwan Lam
- Yuan‑Yuan Li
- James Chung‑Man Ho
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Affiliations: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, SAR, P.R. China
Published online on: July 21, 2017 https://doi.org/10.3892/ol.2017.6646
Pages: 3748-3754

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Abstract

Lung squamous cell carcinoma (SCC) is the second most common subtype of non-small cell lung carcinoma. The anticancer effects of arsenic trioxide (ATO) in lung adenocarcinoma and small‑cell lung cancer have previously been reported; however its effects in SCC remain unclear. An MTT assay and western blot analysis were performed to determine cell viability and protein expression, respectively, in the SK‑MES‑1 and SW900 SCC cell lines following treatment with ATO. Phosphatidylserine externalization, mitochondrial membrane depolarization and cell cycle distribution were studied using flow cytometry and the in vivo effects of ATO on tumour growth were investigated with a xenograft model. The results demonstrated that SK‑MES‑1 and SW900 SCC cells were sensitive to clinically relevant concentrations of ATO. ATO induced apoptosis, mitochondrial membrane depolarization and G2/M arrest. In addition, treatment with ATO resulted in the downregulation of X‑linked inhibitor of apoptosis, B‑cell lymphoma‑2 (Bcl‑2), E2F transcription factor 1 (E2F1), thymidylate synthase and ribonucleotide reductase M1 in addition to the upregulation of Bcl‑2 antagonist/killer protein, cleaved poly ADP‑ribose polymerase and cleaved caspase 3 in a cell‑line specific manner. In the SW900 xenograft model, tumour growth was inhibited by ATO with the formation of apoptotic bodies and downregulation of Bcl‑2 and E2F1. In conclusion, ATO suppresses the growth of SCC in vitro and in vivo.

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