Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway
- J Breast Cancer. 2019 Apr 22;22(2):185-195. doi: 10.4048/jbc.2019.22.e22.
- 1. Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
- 2. Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
- 3. Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan City, Taiwan.
Purpose: Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast Cancer cells.
Methods: Breast Cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed.
Results: Breast Cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin.
Conclusion: Doxorubicin activates the RhoA/MLC pathway and enhances breast Cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.