2. Academic Validation
  3. Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway

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.
Chien-Liang Liu 1 2,  Ming-Jen Chen 1 2,  Jiunn-Chang Lin 1 2,  Chi-Hsin Lin 2 3,  Wen-Chien Huang 1 2,  Shih-Ping Cheng 1 2,  Shan-Na Chen 2,  Yuan-Ching Chang 1 2
Affiliations

Affiliations

  • 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.
PMID: 31281722 DOI: 10.4048/jbc.2019.22.e22
Abstract

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.

Keywords

Breast; Carcinoma; Cell movement; Doxorubicin.

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