Abstract
BackgroundRecent studies have suggested that the Src inhibitor dasatinib preferentially inhibits the growth of breast cancer cells of the basal-like subtype. To clarify this finding and further investigate combined antitumor effects of dasatinib with cytotoxic agents, a panel of breast cancer cell lines of various subtypes was treated with dasatinib and/or chemotherapeutic agents.MethodsSeven human breast cancer cell lines were treated with dasatinib and/or seven chemotherapeutic agents. Effects of the treatments on c-Src activation, cell growth, cell cycle, apoptosis and the proportion of aldehyde dehydrogenase (ALDH) 1-positive cells were examined.ResultsThe 50%-growth inhibitory concentrations (IC50s) of dasatinib were much lower in two basal B cell lines than those in the other cell lines. The IC50s of chemotherapeutic agents were not substantially different among the cell lines. Dasatinib enhanced antitumor activity of etoposide in the basal B cell lines. Dasatinib induced a G1-S blockade with a slight apoptosis, and a combined treatment of dasatinib with etoposide also induced a G1-S blockade in the basal B cell lines. Dasatinib decreased the expression levels of phosphorylated Src in all cell lines. Interestingly, dasatinib significantly decreased the proportion of ALDH1-positive cells in the basal B cell lines but not in the other cell lines.ConclusionsThe present study indicates that dasatinib preferentially inhibits the growth of breast cancer cells of the basal B subtype associated with a significant loss of putative cancer stem cell population. A combined use of dasatinib with etoposide additively inhibits their growth. Further studies targeting breast cancers of the basal B subtype using dasatinib with cytotoxic agents are warranted.
Highlights
Recent studies have suggested that the Src inhibitor dasatinib preferentially inhibits the growth of breast cancer cells of the basal-like subtype
According to the immunohistochemical intrinsic subtypes, the KPL-1 and KPL-3C cell lines were categorized as the luminal A subtype, the BT-474 cell line as the luminal B subtype, the KPL-4 cell line as the HER2positive/estrogen receptor (ER)-negative subtype, and the MDA-MB-231, MDMB-157 and HCC1937 cell lines as the basal-like subtype [3]
To further clarify the potential clinical role of the Src inhibitor dasatinib in breast cancer, we examined the in vitro effects of dasatinib using a panel of human breast cancer cell lines of four different subtypes (Additional file 1)
Summary
Recent studies have suggested that the Src inhibitor dasatinib preferentially inhibits the growth of breast cancer cells of the basal-like subtype. Recent preclinical studies have shown that a multiple tyrosine kinase inhibitor, dasatinib, has a more potent antitumor effect on triple negative/basal-like breast cancer cells than those of other subtypes [5,6]. A series of preclinical and clinical studies have indicated that most triple negative/basal-like breast cancers have dysfunctional BRCA1 or loss of BRCA1 expression [7,8,9]. Preclinical and clinical studies have suggested that triple negative/basal-like breast cancers are sensitive to DNA-damaging agents such as cisplatin (Cis) [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
