Low-dose salinomycin inhibits breast cancer metastasis by repolarizing tumor hijacked macrophages toward the M1 phenotype

Huan Shen, Changquan Calvin Sun, Lichun Kang, Xiaoyue Tan, Peng Shi, Lingyu Wang, Ergang Liu, Junbo Gong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Macrophages are sentinels of the immune system, which are often hijacked by tumor cells to assist tumor growth and metastasis. Herein our results showed that low dose salinomycin (SAL) in the range of 10-50 nM could efficiently induce M1 macrophage polarization in a dose- and time- dependent manner in vitro, with 30 nM SAL being optimal to generate M1-type macrophages from RAW246.7 cells. In animal study, intratumorally injected SAL (50 µg/kg) increased proportion of CD86 cells (by 28.9%), and decreased CD206 cells (by 14.2%) in transplant 4T1 tumors, in comparison with PBS group. Thus it resulted in significant regression in tumor growth (20% tumor inhibition) and pulmonary metastasis (reduced the number of metastatic nodes by 58%) in SAL group, whereas lipopolysaccharide (LPS) and paclitaxel (PTX) groups showed comparable number of metastatic lesions and volume of tumor. LPS treatment could as well lead to inflammatory reactions in tumor with SAL group, but resulted in systemic inflammation (elevated levels of IL-1α, IL-1β and TNF-α in serum), and PTX (10 μg/kg) treatment increased both types of macrophages. For the first time, we employed salinomycin below the dose of direct antitumor activity could effectively prime M1 type macrophage stimulation and regress tumor growth and metastasis.

Original languageEnglish (US)
Article number105629
JournalEuropean Journal of Pharmaceutical Sciences
Volume157
DOIs
StatePublished - Feb 1 2021

Bibliographical note

Funding Information:
This work was financially supported by the Innovative Group Project (No. 21621004) and National Science Foundation of Tianjin (No. 19JCZDJC37500).

Publisher Copyright:
© 2020

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • Salinomycin
  • breast cancer
  • dose-dependent effect
  • inflammation
  • macrophage polarization
  • pulmonary metastasis

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