Inhibition of GLUT-1 expression and the PI3K/Akt pathway to enhance the chemosensitivity of laryngeal carcinoma cells in vitro

Abstract

BackgroundThe mechanism of chemoresistance remains unknown. Here, we investigated if glucose transporter-1 (GLUT-1) and PI3K/Akt pathways are associated with the sensitivity to cisplatin in Hep-2 laryngeal carcinoma cells and whether the inhibition of GLUT-1 and the PI3K/Akt pathways enhances the chemosensitivity of Hep-2 cells.MethodThe effects of inhibiting GLUT-1 by a GLUT-1 siRNA, and PI3K/Akt by Ly294002, on cisplatin-induced effects were assessed in vitro.ResultsGLUT-1 siRNA and cisplatin showed a synergistic effect in inhibiting the proliferation of Hep-2. LY294002 and cisplatin also showed a synergistic effect in inhibiting the proliferation of Hep-2. GLUT-1 siRNA, LY294002 and cisplatin effectively inhibited the mRNA expressions and protein expressions of GLUT-1, Akt, PI3k and HIF-1α in Hep-2 cells. Furthermore, GLUT-1 siRNA and cisplatin demonstrated a synergism to inhibit the mRNA expression of HIF-1α. Moreover, it was found in this study that GLUT-1 siRNA, LY294002 and cisplatin induced the suppression of the cell cycle at G1/G2 and the increasing of apoptosis in Hep-2 cells.ConclusionThis study showed that inhibiting GLUT-1, by a GLUT-1 siRNA and inhibiting PI3K/Akt by Ly294002, could suppress the proliferation of Hep-2 alone and together with cisplatin synergistically, which demonstrated the potentials to treat laryngeal carcinoma in the future therapy. Additionally, the synergistic effect between LY294002 and cisplatin to suppress the proliferation of Hep-2 might not be from GLUT-1, Akt, PI3k and HIF-1α; the synergistic effect between GLUT-1 siRNA and cisplatin to suppress the proliferation of Hep-2 might not be from GLUT-1, Akt and PI3k and might be more or less related to HIF-1α.

Radiosensitizing effects of curcumin alone or combined with GLUT1 siRNA on laryngeal carcinoma cells through AMPK pathway‐induced autophagy

“…GLUT1 expression was significantly increased after irradiation compared to control cells. These results are similar to those of our previous studies 3‐5,28 and suggest a correlation between elevated GLUT1 expression and radioresistance of LC 5,28,29 . As a well‐known antioxidant, curcumin has both radiosensitizing and radioprotective properties.…”

Metabolic Reprogramming and Inflammatory Response Induced by D-Lactate in Bovine Fibroblast-Like Synoviocytes Depends on HIF-1 Activity

“…A dependence on the PI3K/Akt pathway for the expression of pro-inflammatory cytokines, namely IL-6, IL-8, IL-17a, and IL-1β, was also reported by Li et al in synovial fibroblasts isolated from rats with experimental OA ( 77 ). Similarly, in human tumoral cell lines, pharmacological inhibition of the PI3K/Akt pathway was shown to reduce the mRNA expression of Glut-1 ( 78 – 80 ) as well as the protein levels of HIF-1α and PDK-1 ( 81 ).…”

“…Each bar represents the mean ± SEM, n = 5. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. tumoral cell lines, pharmacological inhibition of the PI3K/Akt pathway was shown to reduce the mRNA expression of Glut-1(78)(79)(80) as well as the protein levels of HIF-1α and PDK-1(81).…”

Glucose Transporter 1 and Hypoxia-Inducible Factor 1α is Indicators of Head and Neck Squamous Cell Carcinoma Aggressiveness and Poor Prognosis: A Case Control Study

“…Hypoxia promotes the expression of hypoxia-inducible factor (HIF), which plays an important role in the processes of in ltration, recurrence, and metastasis induced by hypoxia [8][9]. Previous studies also found that the expression of HIF-1α increased and was related to some biological behaviors of laryngeal carcinoma [10][11][12][13]. There have been few reports regarding the relationship between HIF-1α expression and the biological behavior of hypopharyngeal carcinoma.…”