Autophagy inhibition improves the targeted radionuclide therapy efficacy of 131I-FAP-2286 in pancreatic cancer xenografts

作者：Xingyu Liu, Danni Li, Tianbao Ma, Xiu Luo, Peng Ye, Tao Wang, Changjing Zuo, Jianming Cai · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-04958-6 · 被引用次数：10 · 研究领域：Peptidase Inhibition and Analysis、Ubiquitin and proteasome pathways、Autophagy in Disease and Therapy

Abstract Purposes Radiotherapy can induce tumor cell autophagy, which might impair the antitumoral effect. This study aims to investigate the effect of autophagy inhibition on the targeted radionuclide therapy (TRT) efficacy of 131 I-FAP-2286 in pancreatic cancer. Methods Human pancreatic cancer PANC-1 cells were exposed to 131 I-FAP-2286 radiotherapy alone or with the autophagy inhibitor 3-MA. The autophagy level and proliferative activity of PANC-1 cells were analyzed. The pancreatic cancer xenograft-bearing nude mice were established by the co-injection of PANC-1 cells and pancreatic cancer-associated fibroblasts (CAFs), and then were randomly divided into four groups and treated with saline (control group), 3-MA, 131 I-FAP-2286 and 131 I-FAP-2286 + 3-MA, respectively. SPECT/CT imaging was performed to evaluate the bio-distribution of 131 I-FAP-2286 in pancreatic cancer-bearing mice. The therapeutic effect of tumor was evaluated by 18 F-FDG PET/CT imaging, tumor volume measurements, and the hematoxylin and eosin (H&E) staining, and immunohistochemical staining assay of tumor tissues. Results 131 I-FAP-2286 inhibited proliferation and increased the autophagy level of PANC-1 cells in a dose-dependent manner. 3-MA promoted 131 I-FAP-2286-induced apoptosis of PANC-1 cells via suppressing autophagy. SPECT/CT imaging of pancreatic cancer xenograft-bearing nude mice showed that 131 I-FAP-2286 can target the tumor effectively. According to 18 F-FDG PET/CT imaging, the tumor gr...