Contributions
Abstract: PB1715
Type: Publication Only
Background
Acute Myeloid Leukemia (AML) is a heterogenous, clonal hematopoietic malignancy with overproduction of abnormal myeloid progenitors in bone marrow. Although the 7+3 regimen for patients with AML has increased the survival rate, common chemotherapy is not very efficient especially for older patients and the possibility of relapsed and refractory is high which is due to malignant cell called leukemic stem cell. Hence, targeting overexpressed receptors like VEGFR-2 and its related signaling pathway in leukemic blasts is needed.
Aims
So, we aimed to evaluate the cytotoxicity of brivanib alaninate on AML cell lines by inhibiting VEGFR-2 and FGFR signaling pathways.
Methods
In this study, KG1a which has been considered as a drug resistance AML cell line and a leukemic stem cell model, was used for cell culture. Cells were treated with 5 different doses of Brivanib Alaninate (Apexbio company, USA) for 48 and 72 hours and then MTT assay (sigma-Aldrich) was performed to evaluate the viability of these cell lines. Optical densities of each wells were measured at 540 nm wavelength. Finally, annexin V FITC/PI staining to investigate apoptosis effects of Brivanib Alaninate.
Results
Viability of the cells at doses of 0.01, 0.1, 1, 10 and 100 ϻM were 87, 82, 80, 73 and 71 % after 48 hours and 75, 70, 65, 56 and 50 % after 72 hours, respectively. The data showed that IC-50 of the drug is 100 ϻM which was then confirmed with Flowcytometry. The flowcytometry results showed that 31.2% of cell are in late apoptosis and 20.4% of cells in early apoptosis state.
Conclusion
The effective dose of brivanib alaninate for treatment of KG1a cell line is 100 ϻM with 50% cell death after 72 hours treatment. So, targeting two or more dominant signaling pathway and is suggested for target therapy and the use of brivanib alaninate in clinical trials for patients with AML especially in relapse state in recommended.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Myeloid Leukemia, Leukemic Stem Cell, Vascular endothelial growth factor (VEGF)
Abstract: PB1715
Type: Publication Only
Background
Acute Myeloid Leukemia (AML) is a heterogenous, clonal hematopoietic malignancy with overproduction of abnormal myeloid progenitors in bone marrow. Although the 7+3 regimen for patients with AML has increased the survival rate, common chemotherapy is not very efficient especially for older patients and the possibility of relapsed and refractory is high which is due to malignant cell called leukemic stem cell. Hence, targeting overexpressed receptors like VEGFR-2 and its related signaling pathway in leukemic blasts is needed.
Aims
So, we aimed to evaluate the cytotoxicity of brivanib alaninate on AML cell lines by inhibiting VEGFR-2 and FGFR signaling pathways.
Methods
In this study, KG1a which has been considered as a drug resistance AML cell line and a leukemic stem cell model, was used for cell culture. Cells were treated with 5 different doses of Brivanib Alaninate (Apexbio company, USA) for 48 and 72 hours and then MTT assay (sigma-Aldrich) was performed to evaluate the viability of these cell lines. Optical densities of each wells were measured at 540 nm wavelength. Finally, annexin V FITC/PI staining to investigate apoptosis effects of Brivanib Alaninate.
Results
Viability of the cells at doses of 0.01, 0.1, 1, 10 and 100 ϻM were 87, 82, 80, 73 and 71 % after 48 hours and 75, 70, 65, 56 and 50 % after 72 hours, respectively. The data showed that IC-50 of the drug is 100 ϻM which was then confirmed with Flowcytometry. The flowcytometry results showed that 31.2% of cell are in late apoptosis and 20.4% of cells in early apoptosis state.
Conclusion
The effective dose of brivanib alaninate for treatment of KG1a cell line is 100 ϻM with 50% cell death after 72 hours treatment. So, targeting two or more dominant signaling pathway and is suggested for target therapy and the use of brivanib alaninate in clinical trials for patients with AML especially in relapse state in recommended.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Myeloid Leukemia, Leukemic Stem Cell, Vascular endothelial growth factor (VEGF)