Sodium selenite attenuates lung adenocarcinoma progression by repressing SOX2-mediated stemness

• DOI: 10.1007/s00280-018-3561-4
• Publication Date: 2018-03-15T01:44:50Z
• Authors: Weiwei Chen; Jiajia An; Jiwei Guo; Yan Wu; Lijuan Yang; Juanjuan Dai; Kaikai Gong; Shuang Miao; Sichuan Xi; Jing Du
• Keywords: Lung Neoplasms; SOXB1 Transcription Factors; Drug Evaluation, Preclinical; Adenocarcinoma of Lung; Antineoplastic Agents; Zinc Finger Protein GLI1; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Sodium Selenite; 0302 clinical medicine; Cell Line, Tumor; Spheroids, Cellular; Neoplastic Stem Cells; Humans; Cell Proliferation

Sodium selenite (SS) has been widely reported to induce apoptosis in various cancer cell types. However, the underlying molecular mechanisms governing SS-mediated repression of lung cancer stem cells remain largely undefined.In vitro assays of cell proliferation, clonal formation, apoptosis, migration and cancer stemness cell sphere formation were performed to examine the inhibitory effects of SS on lung adenocarcinoma (LAD) cells with or without the overexpression of SRY-related high-mobility-group box 2 (SOX2).SS significantly inhibited cell growth and induced apoptosis in LAD cells in a dose-dependent manner with marginal effects on normal epithelial cell HBEC. SS dramatically repressed expression of SOX2 and its upstream regulator GLI1 and strongly decreased stemness sphere formation in LAD cells at 10 µM. Forced expression of SOX2 significantly buffered anti-cancer effects of SS.Our results demonstrate that SS attenuates lung adenocarcinoma progression by repressing SOX2 and its upstream regulator GLI1, which suggests that SS may be a potential therapeutic drug candidate for lung cancer patients.