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
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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 (OXP) combined with 5-fluorouracil (5-FU) on patient-derived LGSOC cells.
Results
Clinically relevant concentrations of OXP and 5-FU 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 Cip1 , accompanied by reduced pRb phosphorylation, consistent with activation of the p53–p21–pRb pathway. OXP+5-FU also increased senescence-associated β-galactosidase (SA-β-Gal) activity, cellular enlargement and flattening, and reactive oxygen species (ROS) 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 OXP+5-FU primarily arrests rather than kills LGSOC cells and induces a transient senescence-like phenotype and G0/G1-phase arrest by activating the p53–p21–pRb pathway.
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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 https://www.biorxiv.org/content/10.64898/2026.09.22.753519v1
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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 https://www.biorxiv.org/content/10.64898/2026.09.22.753519v1
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