Inhibition of GLUT-1 expression and the PI3K/Akt pathway to enhance the chemosensitivity of laryngeal carcinoma cells in vitro
Authors Jiang T, Zhou ML, Fan J
Received 11 June 2018
Accepted for publication 9 September 2018
Published 6 November 2018 Volume 2018:11 Pages 7865—7872
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 4
Editor who approved publication: Dr William Cho
Tao Jiang,1 Min-Li Zhou,2 Jun Fan3
1Department of Otolaryngology, Yinzhou People’s Hospital of Ningbo City Zhejiang Province, Zhejiang, China; 2Department of Otolaryngology, 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine Zhejiang University, Zhejiang, China
Background: The 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.
Method: The effects of inhibiting GLUT-1 by a GLUT-1 siRNA, and PI3K/Akt by Ly294002, on cisplatin-induced effects were assessed in vitro.
Results: GLUT-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.
Conclusion: This 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.
Keywords: laryngeal carcinoma, RNA interference, glucose transporter-1, PI3K/Akt pathway, cisplatin, chemosensitivity
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