Regorafenib Induces Senescence and Epithelial-Mesenchymal Transition in Colorectal Cancer to Promote Drug Resistance.

ABSTRACT: Potential intrinsic resistance mechanisms to regorafenib were explored after short exposure (3 days) on five CRC cell lines (HCT-116, SW1116, LS-1034, SW480, Caco-2). The observation of senescence-like features led to the investigation of a drug-initiated phenotype switch. Following long-term exposure (12 months) of HCT-116 and SW480 cell lines to regorafenib, we developed resistant models to explore acquired resistance. SW480 cells demonstrated senescent-like properties, including a cell arrest in the late G2/prophase cell cycle stage and a statistically significant decrease in the expression of G1 Cyclin-Dependent Kinase inhibitors and key cell cycle regulators. A specific senescence-associated secretome was also observed. In contrast, HCT-116 treated cells presented early senescent feat

SUBMITTER: Kehagias P 

PROVIDER: S-EPMC9688587 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature