Jiang Tao, Zhou Min-Li, Fan Jun
Department of Otolaryngology, Yinzhou People's Hospital of Ningbo City Zhejiang Province, Zhejiang, China,
Department of Otolaryngology.
Onco Targets Ther. 2018 Nov 6;11:7865-7872. doi: 10.2147/OTT.S176818. eCollection 2018.
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.
The effects of inhibiting GLUT-1 by a GLUT-1 siRNA, and PI3K/Akt by Ly294002, on cisplatin-induced effects were assessed in vitro.
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.
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.
化疗耐药机制尚不清楚。在此，我们研究了葡萄糖转运蛋白1（GLUT-1）和PI3K/Akt信号通路是否与Hep-2喉癌细胞对顺铂的敏感性相关，以及抑制GLUT-1和PI3K/Akt信号通路是否能增强Hep-2细胞的化疗敏感性。
在体外评估GLUT-1小干扰RNA（siRNA）抑制GLUT-1以及LY294002抑制PI3K/Akt对顺铂诱导效应的影响。
GLUT-1 siRNA和顺铂在抑制Hep-2细胞增殖方面显示出协同作用。LY294002和顺铂在抑制Hep-2细胞增殖方面也显示出协同作用。GLUT-1 siRNA、LY294002和顺铂有效抑制了Hep-2细胞中GLUT-1、Akt、PI3k和HIF-1α的mRNA表达和蛋白表达。此外，GLUT-1 siRNA和顺铂在抑制HIF-1α的mRNA表达方面表现出协同作用。而且，本研究发现GLUT-1 siRNA、LY294002和顺铂诱导Hep-2细胞的细胞周期在G1/G2期受到抑制并使细胞凋亡增加。
本研究表明，通过GLUT-1 siRNA抑制GLUT-1以及通过LY294002抑制PI3K/Akt，单独或与顺铂联合使用均可抑制Hep-2细胞增殖，这显示了其在未来喉癌治疗中的潜力。此外，LY294002和顺铂抑制Hep-2细胞增殖的协同作用可能并非源于GLUT-1、Akt、PI3k和HIF-1α；GLUT-1 siRNA和顺铂抑制Hep-2细胞增殖的协同作用可能并非源于GLUT-1、Akt和PI3k，可能与HIF-1α或多或少有关。
