Silence of STAT3 Enhances SNX-2112-induced Apoptosis of Esophageal Cancer Stem Cells

Abstract

Objective To investigate the effect of STAT3 silence on SNX-2112-induced apoptosis of esophageal cancer stem cells. Methods shSTAT3 lentiviral vector was designed and constructed. Esophageal cancer stem cells were transfected with shSTAT3 vector and then these cells were treated by Hsp90 inhibitor SNX-2112. CCK8 assay and soft agar plate assay were employed to evaluate the inhibitory effect of shSTAT3 and SNX-2112 on the viability and proliferation of esophageal cancer stem cells. Flow cytometry assay was used to detect the induction effect of shSTAT3 and SNX-2112 on the apoptosis of esophageal cancer stem cells. The expression levels of Bcl2 and Bax in esophageal cancer stem cells were analyzed by Western blot. Results shSTAT3 significantly silenced the expression of STAT3 at mRNA(P < 0.05) and protein(P < 0.01) levels. shSTAT3 and different concentrations (0.015625, 0.03125, 0.0625, 0.125, 0.25, 0.5, 1.0 μmol/L) of SNX-2112 inhibited notably the viability of cancer stem cells after 24h. And the IC50 value was (0.28±0.01) μmol/L. The colony formation efficiency was decreased after cancer stem cells were treated by shSTAT3 and SNX-2112(P < 0.01). The apoptotic cells and the percentage of subG1 were increased significantly by shSTAT3 and SNX-2112(both P < 0.01). Bcl2 expression was decreased while Bax expression was increased by shSTAT3 and SNX-2112(both P < 0.05). Conclusion Silence of STAT3 enhances SNX-2112-induced apoptosis of esophageal cancer stem cells.

Keywords

• stat3
• hsp90
• snx-2112
• esophageal cancer stem cells