Date of Award

2022

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Walstrom, Katherine

Area of Concentration

Biochemistry

Abstract

Lung cancer is the leading cause of cancer related deaths, and non-small cell lung cancers (NSCLC) make up the majority of cases. EGFR-mutant NSCLC patients have been found to develop resistance to chemotherapeutic agents such as third generation tyrosine kinase inhibitor, osimertinib, over time. This study aimed to determine the effects of CARM1 inhibitors on EGFR-mutant NSCLC cell lines and to assess if a CARM1 inhibitor (CARM1i) shows cooperativity with osimertinib to reduce viability of EGFR-mutant NSCLC cell lines. This study involved a colorimetric thiazolyl blue tetrazolium bromide (MTT) assay to determine cell viability for a series of single and combination dose treatments, Annexin V FITC staining to detect apoptosis, western blot analysis for proteins associated with apoptosis, and senescence-associated beta-galactosidase (SA- β-gal) staining to detect the presence of senescence. Results showed that CARM1i and osimertinib, both singularly and in combination, decreased cell viability in EGFR-mutant NSCLC cell lines. Co-treatment with CARM1i and osimertinib exhibited increased cell death as seen by phase contrast microscopy, cell viability assays, and increased cleavage of PARP1 and caspase 3. Therefore, CARM1 inhibitors are an effective strategy to combat viability of EGFR-mutant NSCLC cell lines. Future studies could be conducted to determine if the use of CARM1 inhibitors can overcome the development of resistance to clinically-used EGFR inhibitors like osimertinib and erlotinib.

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