AUGMENTING CHEMOTHERAPY SENSITIVITY IN COLORECTAL CANCER VIA INHIBITION OF CDC42

Abstract

Colorectal cancer(CRC) remains a major global health issue due to the chemoresistance, such as to doxorubicin(DOX). In this study, we investigated whether Cdc42 inhibitor, CASIN, could enhance the sensitivity of LoVo CRC cell lines to doxorubicin. First, we determined the IC50 of DOX, which was 0.1398 µM in non-resistant(NR) LoVo cells and 0.5281 µM in DOX-resistant(DOX-R) cells. Then, we assessed the cytotoxicity of CASIN, DOX, and their combination(CASIN+DOX) on LoVo cell viability. While CASIN alone had no significant impact on viability, CASIN+DOX treatment significantly reduced cell viability in both NR and DOX-R cancer cell lines, lowering survival to below 10% of control in resistant cells. G-LISA assay results showed no difference in basal Cdc42 activity between NR and DOX-R cells, indicating resistance did not alter Cdc42 activation. Quantification assay of intracellular DOX revealed that CASIN did not increase DOX accumulation, suggesting its chemosensitizing effect is activated independently of drug uptake. These findings demonstrate that CASIN increases DOX cytotoxicity through regulating Cdc42-dependent survival pathways rather than by altering DOX efflux.