Iodine‑125 interstitial brachytherapy reduces tumor growth via Warburg effect inhibition in non‑small cell lung cancer A549 xenografts

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.