Inhibition of TBK1 and IKKε by Amlexanox Synergizes with Bortezomib to Reduce Myeloma Cell Growth
School Name
Home School
Grade Level
12th Grade
Presentation Topic
Biochemistry
Presentation Type
Mentored
Oral Presentation Award
2nd Place
Written Paper Award
3rd Place
Abstract
Multiple myeloma causes increased osteoclast activity and decreased osteoblast formation that results in extensive bone damage. The aim of this study was to explore the potential usefulness of Amlexanox, a TBK1 and IKKε kinase inhibitor that decreases osteoclastogenesis, as a potential therapeutic for MM bone disease. Amlexanox alone slowed the growth of myeloma cell lines. Therefore, this study tested the effects of combining Amlexanox with a current myeloma therapeutic, the protease inhibitor Bortezomib, on myeloma cell growth and apoptosis. First, the effects of a single suboptimal dose of Amlexanox and Bortezomib alone and in combination on five MM cell lines were assessed using CellTiter-Glo assays. This was followed by analyses of a set of total drug concentrations (¼, ½, 1, 2, 4-fold) that maintained a constant ratio of Amlexanox to Bortezomib based on their IC50s to determine whether their combined effect on the myeloma cells was antagonistic, additive, or synergistic. The results of the assay showed that the drugs combined antagonistically at low doses and synergistically from the IC50 up. In addition, the effects of Amlexanox on different stages of bone marrow differentiation to osteoclasts were tested using a TRAP assay. These results showed that the first 48 hours after exposure were the most critical to decrease osteoclast formation. The results of this study suggest that Amlexanox combined with Bortezomib is a potential therapeutic treatment for myeloma patients and the Amlexanox may help to prevent excess osteoclastogenesis in myeloma patients.
Recommended Citation
Davis, Sarah, "Inhibition of TBK1 and IKKε by Amlexanox Synergizes with Bortezomib to Reduce Myeloma Cell Growth" (2017). South Carolina Junior Academy of Science. 8.
https://scholarexchange.furman.edu/scjas/2017/all/8
Location
Wall 118
Start Date
3-25-2017 10:00 AM
Presentation Format
Oral and Written
Group Project
No
Inhibition of TBK1 and IKKε by Amlexanox Synergizes with Bortezomib to Reduce Myeloma Cell Growth
Wall 118
Multiple myeloma causes increased osteoclast activity and decreased osteoblast formation that results in extensive bone damage. The aim of this study was to explore the potential usefulness of Amlexanox, a TBK1 and IKKε kinase inhibitor that decreases osteoclastogenesis, as a potential therapeutic for MM bone disease. Amlexanox alone slowed the growth of myeloma cell lines. Therefore, this study tested the effects of combining Amlexanox with a current myeloma therapeutic, the protease inhibitor Bortezomib, on myeloma cell growth and apoptosis. First, the effects of a single suboptimal dose of Amlexanox and Bortezomib alone and in combination on five MM cell lines were assessed using CellTiter-Glo assays. This was followed by analyses of a set of total drug concentrations (¼, ½, 1, 2, 4-fold) that maintained a constant ratio of Amlexanox to Bortezomib based on their IC50s to determine whether their combined effect on the myeloma cells was antagonistic, additive, or synergistic. The results of the assay showed that the drugs combined antagonistically at low doses and synergistically from the IC50 up. In addition, the effects of Amlexanox on different stages of bone marrow differentiation to osteoclasts were tested using a TRAP assay. These results showed that the first 48 hours after exposure were the most critical to decrease osteoclast formation. The results of this study suggest that Amlexanox combined with Bortezomib is a potential therapeutic treatment for myeloma patients and the Amlexanox may help to prevent excess osteoclastogenesis in myeloma patients.
Mentor
Mentor: Deborah Galson and Quanhong Sun, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute