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Effect of Rapamycin on Canine Mast Cell Cancer Cells Following Radiation

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Title: Effect of Rapamycin on Canine Mast Cell Cancer Cells Following Radiation
Author: Phan, Morla
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: Coomber, Brenda
Abstract: Radiation therapy has been a staple treatment for many cancers, either applied as an adjuvant or a monotherapy. Radiation resistance is an issue, either innate or acquired, that decreases the effectiveness of treatment. Rapamycin has been reported to reduce cancer cell survival following radiation therapy in certain cancers, but the specific mechanism through which this occurs is still unclear. This compound is an inhibitor of mTOR, which is responsible for several essential cell functions such as growth, proliferation and survival. I hypothesized that the inhibition of mTOR via Rapamycin can alter DNA damage response and investigated this using the canine mast cell cancer cell lines MCT-1 and MCT-2. I found that Rapamycin combined with ionizing radiation did not affect clonogenic survival in MCT-1 cells. However, both MCT-1 and MCT-2 cells did respond to radiation by activating mTOR as assessed by western blotting. This technique also revealed that Rapamycin maintained mTOR inhibition even in the presence of radiation. Quantification of DNA strand breaks using the comet assay revealed that the changes in the severity of radiation damage sustained by MCT cells were not statistically significantly different with Rapamycin treatment. Contrary to what is reported for non small cell lung cancer, RNF168 was not found to be a mediator between mTOR and DNA damage response in these mast cell cancer cell lines. The relationship between these two pathways remains unclear.
Date: 2020-04
Rights: Attribution-ShareAlike 4.0 International
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Attribution-ShareAlike 4.0 International Except where otherwise noted, this item's license is described as Attribution-ShareAlike 4.0 International