Oxaliplatin and 5-Fluorouracil induce p53-p21-pRb-associated cell cycle arrest and a transient senescence-like phenotype in patient-derived low-grade serous ovarian cancer cells

Abstract

Objectives Low grade serous ovarian cancer (LGSOC) is characterized by frequent TP53 wild type status and limited responsiveness to conventional chemotherapy. This study investigated the cytotoxic effects of oxaliplatin combined with 5-fluorouracil on patient derived LGSOC cells. Results Clinically relevant concentrations of oxaliplatin and 5-fluorouracil had minimal effects on LGSOC cell viability but markedly reduced cellular proliferation and clonogenic recovery. Combined treatment induced pronounced accumulation of cells in the G0/G1 phase of the cell cycle and increased expression of p53 and p21, accompanied by reduced pRB phosphorylation, consistent with activation of the p53-p21-pRb pathway. Oxaliplatin plus 5-fluorouracil also increased senescence-associated beta-galactosidase activity, cellular enlargement and flattening, and reactive oxygen species production, supporting a senescence-like phenotype. However, after drug withdrawal, treated cells progressively regained proliferative capacity, indicating that the senescence phenotype was transient rather than fully irreversible. Together, these findings show that oxaliplatin plus 5-fluorouracil primarily arrest rather than kill LGSOC cells and induces a transient senescence-like phenotype and G0/G1-phase arrest by activating the p53-p21-pRb pathway.