Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo.
Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo.
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协同抑制 GLUT-1 表达和 PI3K/Akt 信号通路增强体内喉癌异种移植物的放射敏感性
DOI：
10.1371/journal.pone.0143306
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lu ZJ
中科院分区：
文献类型：
--
作者：
Luo XM;Xu B;Zhou ML;Bao YY;Zhou SH;Fan J;Lu ZJ
在本研究中，我们研究了GLUT-1和PI3K/Akt信号在喉癌移植瘤放射抵抗中的作用。评估不同组别移植瘤的体积、重量、放射增敏作用和肿瘤生长抑制率。用TUNEL法检测细胞凋亡率。此外，还检测了移植瘤中GLUT-1、p-Akt和PI3K的mRNA和蛋白水平。X射线照射后LY294002、Wortmannin、Wortmannin+GLUT-1AS-ODN、LY294002+GLUT-1AS-ODN和LY294002+GLUT-1AS-ODN治疗后，肿瘤体积、重量、肿瘤生长速度和肿瘤细胞凋亡率均显著低于10Gy组(p<；0.05)。此外，GLUT-1、p-Akt和PI3K的mRNA和蛋白表达下调。LY294002、LY294002+GLUT-1反义寡核苷酸、Wortmannin和Wortmannin+GLUT-1 AS-ODN的E/O值分别为2.7、1.1、1.8和1.8。综上所述，这些数据表明GLUT-1AS-ODN以及PI3K/Akt信号的抑制剂可能在体内作为喉癌的放射增敏剂。
In the present study, we investigated the role of GLUT-1 and PI3K/Akt signaling in radioresistance of laryngeal carcinoma xenografts. Volume, weight, radiosensitization, and the rate of inhibition of tumor growth in the xenografts were evaluated in different groups. Apoptosis was evaluated by TUNEL assay. In addition, mRNA and protein levels of GLUT-1, p-Akt, and PI3K in the xenografts were measured. Treatment with LY294002, wortmannin, wortmannin plus GLUT-1 AS-ODN, and LY294002 plus GLUT-1 AS-ODN after X-ray irradiation significantly reduced the size and weight of the tumors, rate of tumor growth, and apoptosis in tumors compared to that observed in the 10-Gy group (p<0.05). In addition, mRNA and protein expression of GLUT-1, p-Akt, and PI3K was downregulated. The E/O values of LY294002, LY294002 plus GLUT-1 AS-ODN, wortmannin, and wortmannin plus GLUT-1 AS-ODN were 2.7, 1.1, 1.8, and 1.8, respectively. Taken together, these data indicate that GLUT-1 AS-ODN as well as the inhibitors of PI3K/Akt signaling may act as radiosensitizers of laryngeal carcinoma in vivo.