18F-FDG PET imaging for monitoring the early anti-tumor effect of albendazole on triple-negative breast cancer

Breast Cancer. 2020 May;27(3):372-380. doi: 10.1007/s12282-019-01027-5. Epub 2019 Nov 28.

Abstract

Background: 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 18F-FDG PET imaging remains relatively unexplored.

Methods: 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.

Results: 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 18F-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.

Conclusions: 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, 18F-FDG PET imaging could be used to monitor the early anti-tumor effect of ABZ on MDA-MB-231 tumors.

Keywords: 18F-FDG PET; Albendazole; Glycolysis; MDA-MB-231 cells.

MeSH terms

  • Albendazole / pharmacology*
  • Animals
  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Female
  • Fluorodeoxyglucose F18 / metabolism*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / metabolism
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*
  • Tubulin Modulators / pharmacology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Radiopharmaceuticals
  • Tubulin Modulators
  • Fluorodeoxyglucose F18
  • Albendazole