HOXB9 inhibits proliferation in gastric carcinoma cells via suppression of phosphorylated-Akt and NF-κB-dependent Snail expression

Background: HOXB9 is a homeobox transcription factor which plays an important role in carcinoma development. This protein has been shown to inhibit cancer cell proliferation. However, the mechanisms that underpin HOXB9-mediated inhibition of cellular proliferation remain to be elucidated. Methods: In this study, two gastric cancer cell lines, SGC7901 and MKN45, were transfected with plasmids pLVX-HOXB9 and shHOXB9. These transfections resulted in the over-expression of the HOXB9 gene in the SGC7901/HOXB9 cells and knockdown of the HOXB9 gene in the MKN45/shHOXB9 cells. Results: Over-expression of the HOXB9 gene in the SGC7901/HOXB9 cells caused an increase in the apoptotic rate and a concomitant reduction in metastatic ability compared with the knocked-down MKN45/shHOXB9 cells. Moreover, a reduction in the expression of the phosphorylated-Akt protein was observed in the SGC7901/HOXB9 cells, while an increase in expression of the same protein was observed in the MKN45/shHOXB9 cells. We also observed that HOXB9 mediated a reduction in both NF-kappa B and N-cadherin and Snail protein expression. Conversely, HOXB9 caused an increase in the expression of E-cadherin. Conclusions: In summary, this study reports that HOXB9 can suppress both phosphorylated-Akt expression and NF-kappa B activity. The latter phenomenon affects Snail protein expression and the inhibition of gastric carcinoma proliferation. (C) 2018 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.