Degree Type

Creative Component

Semester of Graduation

Fall 2018

Department

Biomedical Sciences

First Major Professor

Jonathan Mochel

Degree(s)

Master of Science (MS)

Major(s)

Biomedical Sciences

Abstract

Colon cancer is the third leading type of cancer diagnosis in the United States (Siegel et al, 2017). Common treatments include chemotherapy, which can be toxic to the patient and produce multiple adverse side effects(Sarkar, 2008). Combination therapies with chemotherapy drugs and other compounds have been reported to decrease tumor growth in breast and colon cancer by increasing efficacy of chemotherapeutic agents at lower doses, thus reducing off-target adverse effects(Borcherding et al, 2015; Chen et al 2017). Both activation of Nrf2, a transcription factor that induces expression of anti-oxidant genes, and dopamine receptor agonists, have been shown to reduce tumor growth in multiple cancer types (Borcherding et al, 2015; Melba et al, 2013). Thus, we examined whether combining a common chemotherapy drug, Doxorubicin, with a Nrf2 activator, CDDO-ME, or a dopamine-type-1 receptor agonist, Fenoldopam, improved efficacy of chemotherapy. Treatment of HT29 and HCT116 colorectal cancer cells in vitro with or CDDO-ME in conjunction with Doxorubicin augmented the effects of Doxorubicin alone, as determined by MTT assay. The results support that Doxorubicin had an effect on both cell lines above concentrations of 100 nM. However, Fenoldopam, a dopamine-type-1 receptor agonist, did not significantly affect cell viability. Therefore, the effects of Doxorubicin may be achieved at a lower dose when administered with CDDO-ME.

Copyright Owner

The Authors

File Format

application/pdf

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