hENT1 reverses chemoresistance by regulating glycolysis in pancreatic cancer
hENT1 reverses chemoresistance by regulating glycolysis in pancreatic cancer
复制标题
hENT1 通过调节胰腺癌中的糖酵解来逆转化疗耐药性。
DOI：
10.1016/j.canlet.2020.03.015
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发表时间：
2020-06-01
期刊：
影响因子：
9.7
通讯作者：
Li, Biao
中科院分区：
文献类型：
--
作者：
Xi, Yun;Yuan, Peng;Li, Biao
吉西他滨（GEM）化疗作为胰腺癌的一线治疗方案，往往会引起耐药性，最终恶化胰腺癌患者的预后。我们前期的研究表明胰腺癌进展与糖代谢密切相关，尤其是在化疗耐药阶段，凸显了F-18-FDG PET双时相成像在胰腺癌早期检测中应用的重要性。我们推测糖酵解参与了胰腺癌化疗耐药性的发展。在本文中，我们想要确定操纵胰腺癌细胞中的 hENT1 表达是否可以逆转 GEM 化疗耐药性，以及在此过程中是否涉及葡萄糖转运和糖酵解。我们发现 hENT1 通过抑制胰腺癌中的糖酵解和改变 HIF-1 α 介导的葡萄糖转运来逆转 GEM 诱导的耐药性。我们的研究结果还表明，第4次化疗后的F-18-FDG PET双时相成像可以准确识别耐药胰腺肿瘤并改善hENT1逆转治疗。我们的研究结果强调，从治疗开始时动态观察（保留指数）RI 变化也有助于评估治疗效果。
Gemcitabine (GEM) chemotherapy, as the first-line regimen for pancreatic cancer, tends to induce drug resistance, which ultimately worsens the prognosis of patients with pancreatic cancer. Our previous study indicated a close correlation between pancreatic cancer progression and glucose metabolism, especially at the chemoresistant stage, highlighting the importance of the application of F-18-FDG PET dual-phase imaging in the early detection of pancreatic cancer. We speculate that glycolysis, participates in the development of chemoresistance in pancreatic cancer. In this article, we wanted to determine whether manipulating hENT1 expression in pancreatic cancer cells can reverse GEM chemoresistance and whether glucose transport and glycolysis are involved during this process. We found that hENT1 reversed GEM-induced drug resistance by inhibiting glycolysis and altering glucose transport mediated by HIF-1 alpha in pancreatic cancer. Our findings also suggest that F-18-FDG PET dual-phase imaging after the 4th chemotherapy treatment can accurately identify drug-resistant pancreatic tumors and improve hENT1 reversal therapy. Our findings highlight that the dynamic observation of (retention index) RI changes from the beginning of treatment can also be helpful for evaluating the therapeutic effect.