J Breast Cancer.  2019 Jun;22(2):185-195. 10.4048/jbc.2019.22.e22.

Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway

Affiliations
  • 1Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan. changyc@mmh.org.tw
  • 2Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
  • 3Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan City, Taiwan.

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.

Keyword

Breast; Carcinoma; Cell movement; Doxorubicin
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