Department of Nuclear Medicine, First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Breast Cancer. 2020 May;27(3):372-380. doi: 10.1007/s12282-019-01027-5. Epub 2019 Nov 28.
Multiple studies have indicated that albendazole (ABZ) can disrupt the microtubule in worms and have anti-tumor potential in a variety of tumors. However, the therapeutic effect of ABZ on triple-negative breast cancer (TNBC) is largely unknown, and the therapeutic evaluation of ABZ by F-FDG PET imaging remains relatively unexplored.
The effects of ABZ on TNBC cell lines (MDA-MB-231 cells) were investigated in vitro using MTT, wound-healing, transwell migration, flow cytometry and Western blotting analyses. In vivo treatment was conducted in an MDA-MB-231 tumor-bearing nude mouse model. Mouse body weight loss was also evaluated. PET imaging was performed before and after 3 days of treatment. Tumor tissues were harvested for immunofluorescence analysis.
ABZ treatment inhibited the proliferation and migration and triggered the apoptosis in MDA-MB-231 cells. Furthermore, Western blotting analysis showed that ABZ induced the apoptosis in MDA-MB-231 cells via GLUT1/AMPK/P53 signaling pathway. Long-term treatment studies found that the tumor volume of the treatment group was smaller compared with the control group, and the survival time was prolonged. In vivo F-FDG PET imaging showed that 3-day ABZ treatment reduced standardized uptake value (SUV) values in MDA-MB-231 xenografts compared with the controls, and immunofluorescence analysis showed more TUNEL-positive cells in the ABZ-treated mice.
Our study suggested that ABZ induced the apoptosis of MDA-MB-231 cells by inhibiting glucose uptake, and it could be considered as a potential drug for TNBC cells. Moreover, F-FDG PET imaging could be used to monitor the early anti-tumor effect of ABZ on MDA-MB-231 tumors.
多项研究表明，阿苯达唑（ABZ）可破坏蠕虫中的微管，并在多种肿瘤中具有抗肿瘤潜能。然而，ABZ 对三阴性乳腺癌（TNBC）的治疗效果在很大程度上尚不清楚，且 F-FDG PET 成像对 ABZ 的治疗评估仍相对未知。
采用 MTT、划痕愈合、Transwell 迁移、流式细胞术和 Western blot 分析等方法，在体外研究 ABZ 对 TNBC 细胞系（MDA-MB-231 细胞）的影响。在 MDA-MB-231 荷瘤裸鼠模型中进行体内治疗，并评估小鼠体重减轻情况。治疗前和治疗 3 天后进行 PET 成像。采集肿瘤组织进行免疫荧光分析。
ABZ 处理抑制了 MDA-MB-231 细胞的增殖和迁移，并触发了其凋亡。此外，Western blot 分析显示，ABZ 通过 GLUT1/AMPK/P53 信号通路诱导 MDA-MB-231 细胞凋亡。长期治疗研究发现，与对照组相比，治疗组的肿瘤体积较小，生存时间延长。体内 F-FDG PET 成像显示，与对照组相比，3 天 ABZ 治疗降低了 MDA-MB-231 异种移植瘤的标准化摄取值（SUV）值，免疫荧光分析显示 ABZ 治疗组的 TUNEL 阳性细胞更多。
本研究表明，ABZ 通过抑制葡萄糖摄取诱导 MDA-MB-231 细胞凋亡，可考虑将其作为治疗 TNBC 细胞的潜在药物。此外，F-FDG PET 成像可用于监测 ABZ 对 MDA-MB-231 肿瘤的早期抗肿瘤作用。
