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Πέμπτη 15 Μαρτίου 2018

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

Abstract

Purpose

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.

Methods

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).

Results

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.

Conclusions

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.



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