Zhang Jun, Zhu Yangjun, Dong Mengjie, Yang Jun, Weng Wanwen, Teng Lisong
Department of Nuclear Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Department of Ultrasonography, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Oncol Lett. 2018 Nov;16(5):5969-5977. doi: 10.3892/ol.2018.9346. Epub 2018 Aug 21.
Iodine-125 interstitial brachytherapy (125I-IBT) is an alternative and effective treatment option for unresectable non-small cell lung cancer (NSCLC), and the Warburg effect is a determinant of tumor growth. The present study aimed to explore the influence of 125I-IBT on tumor growth and the Warburg effect, and the potential mechanisms underlying NSCLC progression. Mice with A549 cell xenografts were evenly divided into a control group without 125I-IBT, and three treatment groups receiving 125I-IBT with 20, 40 and 60 Gy. Tumor volume (TV), maximum standardized uptake value (SUVmax) determined by 18F-fluorodeoxyglucose (18F-FDG) micro-positron emission tomography/computed tomography and mean optical density (MOD) of mammalian target of rapamycin (mTOR), c-Myc, hypoxia inducible factor-1α (HIF-1α) and glucose transporter 1 (GLUT1) staining were compared among groups. Tumor inhibition rate (TIR), 18F-FDG uptake attenuation rate (FUAR) and expression suppression rate (ESR) were also calculated on day 14 and 28. The results demonstrated that the mean TV in the 60 and 40 Gy groups was smaller compared with the control TVs since days 14 and 16, respectively. The mean SUVmax value of the 60 Gy group at day 14, and all treatment group SUVmax values at day 28 were lower compared with the controls. In addition, the MOD of mTOR and GLUT1 was lower in the 60 Gy group, compared with the other groups, and c-Myc and HIF-1α values were lower in the 40 and 60 Gy groups, compared with the control and 20 Gy group (P<0.05). SUVmax positively correlated to TV (day 14, r=0.711; day 28, r=0.586) and the MOD of c-Myc and GLUT1 (r=0.621 and 0.546, respectively; P<0.01). Furthermore, dose dependent increases were observed for TIR, FUAR and ESR. In conclusion, 125I-IBT reduced tumor growth by inhibiting the Warburg effect, which may have resulted from downregulation of mTOR, c-Myc, HIF-1α and GLUT1 expression, particularly c-Myc and GLUT1, in NSCLC A549 ×enografts.
碘-125组织间近距离放射治疗（125I-IBT）是不可切除非小细胞肺癌（NSCLC）的一种替代且有效的治疗选择，而瓦伯格效应是肿瘤生长的一个决定因素。本研究旨在探讨125I-IBT对肿瘤生长和瓦伯格效应的影响，以及NSCLC进展的潜在机制。将A549细胞异种移植小鼠平均分为未接受125I-IBT的对照组和接受20、40和60 Gy 125I-IBT的三个治疗组。比较各组间的肿瘤体积（TV）、由18F-氟脱氧葡萄糖（18F-FDG）微型正电子发射断层扫描/计算机断层扫描测定的最大标准化摄取值（SUVmax）以及雷帕霉素哺乳动物靶蛋白（mTOR）、c-Myc、缺氧诱导因子-1α（HIF-1α）和葡萄糖转运蛋白1（GLUT1）染色的平均光密度（MOD）。在第14天和第28天还计算了肿瘤抑制率（TIR）、18F-FDG摄取衰减率（FUAR）和表达抑制率（ESR）。结果表明，60 Gy组和40 Gy组的平均TV分别自第14天和第16天起比对照组的TV小。60 Gy组在第14天的平均SUVmax值以及所有治疗组在第28天的SUVmax值均低于对照组。此外，60 Gy组中mTOR和GLUT1的MOD低于其他组，40和60 Gy组中c-Myc和HIF-1α值低于对照组和20 Gy组（P<0.05）。SUVmax与TV（第14天，r=0.711；第28天，r=0.586）以及c-Myc和GLUT1的MOD（分别为r=0.621和0.546；P<0.01）呈正相关。此外，观察到TIR、FUAR和ESR呈剂量依赖性增加。总之，125I-IBT通过抑制瓦伯格效应减少肿瘤生长，这可能是由于NSCLC A549异种移植瘤中mTOR、c-Myc、HIF-1α和GLUT1表达下调，尤其是c-Myc和GLUT1。
