Honors Theses and Capstones

Date of Award

Spring 2025

Project Type

Senior Honors Thesis

College or School

COLSA

Department

Molecular, Cellular, and Biomedical Sciences

Program or Major

Biochemistry, Molecular and Cellular Biology

Degree Name

Bachelor of Science

First Advisor

Sarah Walker

Abstract

Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer and lacks the three commonly targeted receptors in breast cancer treatments. As a result of a lack of targetable receptors, the standard of care remains to be harsh chemotherapy treatments that often are successful in early TNBC cases but often result in relapsed TNBC. In addition to high rates of recurrence, TNBC is known for its aggressive metastasis and chemoresistance. Within TNBC, the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) is constitutively active and increases proliferation, and metastasis, and plays a role in chemoresistance. Previously in the Walker lab, an undergraduate student identified several potential STAT3 inhibiting drugs, including cilengitide and TWS-119, among a few others. In this thesis, research was done to 1) identify the native protein levels of active and total STAT3 in cilengitide- and TWS-119- resistant MDA-MB-231 and Hs578T TNBC cells and evaluate the viability, migration, and invasion abilities of these resistant cells; and 2) identify the effects of the other potential STAT3 inhibitors on STAT3 protein levels, and evaluate the viability, migration, and invasion abilities of MDA-MB-231 cells with these monotherapies. Resistant cells showed reduced viability over an 8-day period. TWS-119 resistant MDA-MB-231 cells were resistant to the migration effects of TWS-119, but not to a general chemotherapy agent. Additionally, there was an inhibition of cellular invasion of TWS-119 resistant 3D TNBC cells, and erratic invasion of cilengitide resistant 3D TNBC cells. The other potential STAT3 inhibitors significantly decreased cellular viability in TNBC cells but had no effect on TNBC 2D migration. However, they inhibited or reduced 3D invasion. More research needs to be done to conclude the effects of TWS-119 and cilengitide resistance on viability in both the 2D and 3D models, and to identify the effects of resistance and effects of the other potential STAT3 inhibitors on STAT3 levels.

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