Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway
- Author:
Chien Liang LIU
1
;
Ming Jen CHEN
;
Jiunn Chang LIN
;
Chi Hsin LIN
;
Wen Chien HUANG
;
Shih Ping CHENG
;
Shan Na CHEN
;
Yuan Ching CHANG
Author Information
- Publication Type:Original Article
- Keywords: Breast; Carcinoma; Cell movement; Doxorubicin
- MeSH: Blotting, Western; Breast Neoplasms; Breast; Cell Movement; Doxorubicin; Myosin Light Chains; Paclitaxel; Phenotype; Phosphorylation; Up-Regulation
- From:Journal of Breast Cancer 2019;22(2):185-195
- CountryRepublic of Korea
- Language:English
- 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.
