Figure 2 from Targeting the Glucose–Insulin Link in Head and Neck Squamous Cell Carcinoma Induces Cytotoxic Oxidative Stress and Inhibits Cancer Growth

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Abstract
GLUT1 ablation attenuates tumorigenesis in 4NQO-induced mouse model of human HNSCC. A, Schematic showing timeline for treatment of mice with 4NQO. 4NQO was administered in drinking water for 8 weeks and replaced with normal drinking water for the remainder of the study. Tongues were collected every 2 weeks after the first exposure to 4NQO for analyses. For Cre-mediated GLUT1 ablation in basal epithelial cells, tamoxifen was injected (100 mg/kg i.p. daily for 5 consecutive days) 4 weeks after the final administration of 4NQO. Tumors were harvested 4 weeks after the final tamoxifen injection. B, Representative IHC analyses of GLUT1 expression in CK5+ and p63+ basal epithelial cells of untreated and 4NQO-treated mice. C, Representative images of tumor-bearing tongues from 4NQO-treated mice; black arrowheads depict squamous tongue tumors (left). Graph shows quantification of the number of visible tongue tumors identified in 4NQO-treated WT and Krt5+ basal epithelial–specific GLUT1 CKO mice (n = 6 for each group). Mann–Whitney U test. P = 0.06 (right). D, Representative H&E images of 4NQO-treated WT and CKO mouse tongues. Arrows depict 4NQO-induced squamous tumors (left). Graph shows quantification of 4NQO-induced tongue tumor area (μm2) in GLUT1 WT and CKO mice (n = 6 for each group). Mann–Whitney U test. **, P < 0.01 (right). E, Representative co-immunofluorescent staining of GLUT1 and p63 in 4NQO-induced squamous tongue tumors of GLUT1 WT and GLUT1 CKO mice. DAPI, 4',6-diamidino-2-phenylindole. F, Representative IHC analyses of p63, GLUT1, and Ki67 expression in 4NQO-induced squamous tongue tumors. All error bars represent mean ± SEM. All scale bars, 1 mm unless otherwise noted. H&E, hematoxylin and eosin; KO, knockout.