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AuthorKheraldine, Hadeel
AuthorGupta, Ishita
AuthorCyprian, Farhan Sachal
AuthorVranic, Semir
AuthorAl-Farsi, Halema F
AuthorMerhi, Maysaloun
AuthorDermime, Said
AuthorAl Moustafa, Ala-Eddin
Available date2024-04-28T08:28:45Z
Publication Date2024-03-02
Publication NameCancer Cell International
Identifierhttp://dx.doi.org/10.1186/s12935-023-03195-z
CitationKheraldine, H., Gupta, I., Cyprian, F. S., Vranic, S., Al-Farsi, H. F., Merhi, M., ... & Al Moustafa, A. E. (2024). Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways. Cancer Cell International, 24(1), 1-15.
ISSN1475-2867
URIhttp://hdl.handle.net/10576/54305
AbstractRecent investigations have reported the benefits of using a tyrosine kinase inhibitor, dasatinib (DA), as well as programmed death-ligand 1 (PD-L1) inhibitors in the management of several solid tumors, including breast cancer. Nevertheless, the outcome of the combination of these inhibitors on HER2-positive breast cancer is not explored yet. Herein, we investigated the impact of DA and PD-L1 inhibitor (BMS-202) combination on HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data reveal that the combination significantly inhibits cell viability of both cancer cell lines as compared to monotreatment. Moreover, the combination inhibits epithelial-mesenchymal transition (EMT) progression and reduces cancer cell invasion by restoring E-cadherin and β-catenin expressions and loss of vimentin, major biomarkers of EMT. Additionally, the combination reduces the colony formation of both cell lines in comparison with their matched control. Also, the combination considerably inhibits the angiogenesis of the chorioallantoic membrane model compared with monotreatment. Molecular pathway analysis of treated cells shows that this combination blocks HER2, AKT, β-catenin, and JNK1/2/3 activities. Our findings implicate that a combination of DA and BMS-202 could have a significant impact on the management of HER2-positive breast cancer.
SponsorThis work was funded by Qatar University, grant number # QUCP-CMED-22/23–529.
Languageen
PublisherSpringer Nature
SubjectDasatinib
EMT
HER2-positive breast cancer
Invasion
PD-1/PD-L1
TitleTargeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways.
TypeArticle
Pagination1-15
Issue Number1
Volume Number24
dc.accessType Open Access


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