Tumour Growth-Suppressive Effect of Arsenic Trioxide in Squamous Cell Lung Carcinoma

Abstract

Squamous cell lung carcinoma (SCC) is the second commonest subtype of non-small cell lung carcinoma. The anticancer effects of arsenic trioxide (ATO) in lung adenocarcinoma and small cell lung carcinoma have been reported while in SCC are unknown. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Western blot were used to determine cell viability and protein expression respectively. Phosphatidylserine externalization, mitochondrial membrane depolarization and cell cycle distribution were studied using flow cytometry. The in vivo effect of ATO was investigated with a xenograft model. SK-MES-1 and SW900 SCC cells were sensitive to clinically relevant concentrations of ATO. ATO induced apoptosis, mitochondrial membrane depolarization, G2/M arrest, downregulation of XIAP, Bcl-2, E2F1, thymidylate synthase and RRM1 as well as upregulation of Bak, cleaved PARP and cleaved caspase 3 in a cell-line specific manner. In SW900 xenograft model, tumour growth was inhibited by ATO with formation of apoptotic bodies and downregulation of Bcl-2 and E2F1. In conclusion, ATO suppressed growth of SCC in vitro and in vivo.