Inhibiting GLUT-1 expression and PI3K/Akt signaling using apigenin improves the radiosensitivity of laryngeal carcinoma in vivo
Inhibiting GLUT-1 expression and PI3K/Akt signaling using apigenin improves the radiosensitivity of laryngeal carcinoma in vivo
复制标题
使用芹菜素抑制 GLUT-1 表达和 PI3K/Akt 信号传导可改善体内喉癌的放射敏感性。
DOI：
10.3892/or.2015.4158
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发表时间：
2015-10-01
期刊：
影响因子：
4.2
通讯作者：
Huang, Ya-Ping
中科院分区：
文献类型：
--
作者：
Bao, Yang-Yang;Zhou, Shui-Hong;Huang, Ya-Ping
低氧是喉癌放射抵抗的重要因素。葡萄糖转运蛋白-1（GLUT-1）是恶性肿瘤（包括喉癌）的重要缺氧标志物。芹菜素是一种具有潜在抗癌作用的天然植物雌激素类黄酮。各种研究已经报道芹菜素降低GLUT-1表达的作用涉及PI 3 K/Akt通路的下调。因此，芹菜素可能通过PI 3 K/Akt途径抑制GLUT-1的表达，从而提高喉癌的放射敏感性。观察芹菜素或反义寡核苷酸（AS-ODNs）对GLUT-1和PI 3 K/Akt通路相关因子表达的影响。通过移植瘤体积、移植瘤重量和细胞凋亡检测来确定放射敏感性。结果表明，芹菜素或芹菜素与GLUT-1 AS-ODNs联合应用可提高移植瘤的放射敏感性。芹菜素或芹菜素与GLUT-1合用可降低X射线照射后GLUT-1、Akt和PI 3 K mRNA的表达。我们在蛋白质水平上发现了类似的结果。结果提示，芹菜素抑制异种移植瘤生长和增强异种移植瘤放射敏感性的作用可能与抑制GLUT-1表达有关，其机制可能是通过PI 3 K/Akt途径实现的。此外，芹菜素可能通过相同的机制增强GLUT-1 AS-ODNs的作用。
Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is an important hypoxic marker in malignant tumors, including laryngeal carcinoma. Apigenin is a natural phytoestrogen flavonoid that has potential anticancer effects. Various studies have reported that the effects of apigenin on lowering GLUT-1 expression were involved in downregulation of the PI3K/Akt pathway. Thus, apigenin may improve the radiosensitivity of laryngeal carcinoma by suppressing the expression of GLUT-1 via the PI3K/Akt pathway. The effect of GLUT-1 and PI3K/Akt pathway-related factor expressions by apigenin or antisense oligonucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vivo was assessed. The xenograft volume, xenograft weight and apoptosis detection were performed to determine radiosensitivity. The results showed that apigenin or apigenin plus GLUT-1 AS-ODNs improved the radiosensitivity of xenografts. Apigenin or apigenin plus GLUT-1 reduced the expression of GLUT-1, Akt, and PI3K mRNA after X-ray radiation. We found similar results at the protein level. The results suggest that the effects of apigenin on inhibiting xenograft growth and enhancing xenograft radiosensitivity may be associated with suppressing the expression of GLUT-1 via the PI3K/Akt pathway. In addition, apigenin may enhance the effects of GLUT-1 AS-ODNs via the same mechanism.