The Combination of Dasatinib and PD L1 inhibitor prevents the progression of epithelial mesenchymal transition and dramatically blocks cell invasion of HER2 positive breast cancer cells
المؤلف | Kheraldine, Hadeel |
المؤلف | Gupta, Ishita |
المؤلف | Cyprian, Farhan |
المؤلف | Vranic, Semir |
المؤلف | Al Moustafa, Ala-Eddin |
تاريخ الإتاحة | 2021-10-18T08:15:38Z |
تاريخ النشر | 2021 |
اسم المنشور | Qatar University Annual Research an Exhibition 2021 (quarfe) |
الاقتباس | Kheraldine H., Gupta I., Cyprian F., Vranic S., Al-Moustafa A. E., "The Combination of Dasatinib and PD L1 inhibitor prevents the progression of epithelial mesenchymal transition and dramatically blocks cell invasion of HER2 positive breast cancer cells", Qatar University Annual Research Forum and Exhibition (QUARFE 2021), Doha, 20 October 2021, https://doi.org/10.29117/quarfe.2021.0105 |
الملخص | Introduction: Both Dasatinib (DA), a tyrosine kinase inhibitor that is used for targeted cancer therapy, and programmed death-ligand 1 (PD-1/PD-L1) inhibitor that is an immune checkpoint therapy, play a vital role in the management of several types of solid tumors, including breast. Nevertheless, the combined outcome of DA and PD-1/PD-L1 inhibitors in human carcinomas has not been explored yet. Materials and methods: We herein compared the individual impact of DA and PD-1/PD-L1 inhibitors (BMS-202) with their combination on two human HER2-positive breast cancer cell lines, SKBR3 and ZR75. Results: Our data revealed that the combination of DA and BMS-202 significantly inhibits cell proliferation in both cell lines as compared to mono treatment and/or untreated cells. Moreover, we observed that combination treatment prevents the progression of "epithelial-mesenchymal transition" (EMT), which is a hallmark of cell invasion and cancer progression. Our data reveal that DA and BMS-202 together dramatically inhibit cell invasion of SKBR3 and ZR75 cells; this is accompanied by the up-regulation of E-cadherin and its restoration along with b-catenin on the cell membrane and its undercoat, respectively, in addition to the downregulation of vimentin, which are major markers of EMT. Additionally, we found that the synergistic treatment of DA and BMS-202 inhibits colony formation of both cell lines in comparison with their matched control. Conclusion: Our findings implicate that, in comparison to monotreatment, combination of DA and BMS-202 could have a significant impact on the management of HER2-positive breast cancer via HER2 inactivation and specifically b-catenin signaling pathways. |
اللغة | en |
الناشر | Qatar University Press |
الموضوع | Dasatinib PD-1/PD-L1 HER2-positive breast cancer EMT |
النوع | Poster |
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