Targeting Wnt Activity in HCT116 Cells Can Restore Sensitivity to Doxorubicin Resistant Cells — 74a — Abigail Goebel, Devin Messer, Abigail Renner

The Wnt signaling pathway governs crucial aspects of cellular processes such as development, differentiation, regeneration, and functioning, including the mesenchymal  transition observed in many cancer cell lines. This transition involves the loss of cell polarity and cell-cell adhesion, transforming cells into mesenchymal stem-like states  characterized by enhanced motility, drug resistance, tumor growth, and potential for  clinical relapse. In the context of colon cancer, particularly in the HCT116 cell line,  dysregulated Wnt signaling is frequently observed due to mutations in key pathway  genes. This dysregulated pathway plays a critical role in tumorigenesis and progression  of colorectal cancer, making HCT116 cells a valuable model for studying Wnt signaling  and developing targeted therapies. We aimed to investigate the role of Wnt signaling  in these dysregulated pathways utilizing HCT116 cells. In this study, we report that  doxorubicin-resistant HCT116 cells exhibit enhancement of many mesenchymal cell  characteristics including increased proliferation, motility, anchorage-independent growth,  and drug resistance. We further demonstrate that sensitivity to doxorubicin can be  restored to resistant cells by targeting Wnt activity with a small molecule (Xav). This  study explored the modulation of Wnt activity in HCT116 cells through exposure to  toxins and chemotherapy drugs, offering insights into mechanisms of drug resistance and  potential strategies for therapeutic intervention.

Black Hills State University
Dr. Matthew Pawlus