Role and mechanism of Glut-1 and H+/K+-ATPase expression in pepsin-induced development of vocal cord leukoplakia

Abstract

Abstract Purpose We investigated the role of Glut-1 and H + /K + -ATPase expression in pepsin-induced development of human vocal cord leukoplakia cells (HVCLCs). Next, we analyzed the relationship between Glut-1 and H + /K + -ATPase expression with the clinicopathological features of laryngeal carcinoma. Methods Glut-1 and H + /K + -ATPase expression levels in HVCLCs were determined after treatment with artificial gastric juice containing pepsin and laryngeal carcinoma tissues. Results Exposure to pepsin-containing artificial gastric juice significantly enhanced the migration and proliferation of VSCLCs in a time-dependent manner. The apoptotic rate of VSCLCs decreased over time after exposure to pepsin and reached a nadir on day 7 ( p < 0.01). With increasing duration of exposure to pepsin, the proportion of VSCLCs in G0/G1 phase decreased and the proportions in the S and G2/M phases significantly increased ( p < 0.05). After treatment with pepsin-containing artificial gastric juice, RT-PCR and Western blotting showed that the expression of Glut-1 and H + /K + -ATPase α, β significantly increased in HVCLCs compared to in the absence of pepsin ( p < 0.05). The expression of Glut-1 and H + /K + -ATPase α, β gradually increased from vocal cord leukoplakia (VLC) to laryngeal carcinoma ( p < 0.05). Lentivirus-mediated inhibition of Glut-1 expression in VCL significantly inhibited the cells’ migration and proliferation ( p < 0.05) but enhanced their apoptosis ( p < 0.05). Also, inhibition of Glut-1 expression resulted in an increased proportion of cells in G0/G1 phase and a significantly decreased proportion in G2/M phase ( p < 0.05). Conclusions Elevated Glut-1 expression may promote the development of VCL by upregulating laryngeal H + /K + -ATPase expression to reactivate absorbed pepsin, thus damaging the laryngeal mucosa.

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