Low‑grade serous ovarian cancer (LGSOC) is frequently TP53 wild type and typically responds poorly to conventional chemotherapy. This preclinical study evaluated the cellular effects of combining oxaliplatin and 5‑fluorouracil on patient‑derived LGSOC cells. The principal aim was to determine whether the combination is cytotoxic or cytostatic and to characterize associated molecular and phenotypic changes.
At clinically relevant concentrations, the oxaliplatin plus 5‑fluorouracil combination produced only minimal reductions in overall cell viability. In contrast, the treatment markedly reduced measures of cell proliferation and impaired clonogenic recovery. These results indicate that the drug regimen primarily limits proliferative capacity rather than causing widespread immediate cell death in the tested LGSOC cultures.
Combined treatment led to pronounced accumulation of cells in the G0/G1 phase of the cell cycle, consistent with growth arrest. Molecular analysis showed increased expression of p53 and p21 together with reduced phosphorylation of pRb. This pattern aligns with activation of the p53‑p21‑pRb axis as the operative mechanism for enforcing G0/G1 arrest in these TP53 wild‑type LGSOC cells.
Following oxaliplatin plus 5‑fluorouracil exposure, treated cells displayed multiple features associated with cellular senescence. Observed changes included increased activity of senescence‑associated β‑galactosidase, enlargement and flattening of cell morphology, and elevated reactive oxygen species (ROS) production. Collectively, these readouts support the interpretation that the drug combination induces a senescence‑like phenotype in LGSOC cells.
Although treated cells adopted senescence‑associated markers and an arrest phenotype during exposure, the arrest was not permanently fixed. After drug withdrawal, cells progressively regained proliferative capacity and clonogenic potential. The authors therefore characterize the induced state as transient and senescence‑like rather than fully irreversible terminal senescence.
The reported data indicate that in patient‑derived LGSOC cells, oxaliplatin plus 5‑fluorouracil function predominantly as cytostatic agents, enforcing G0/G1 arrest via the p53‑p21‑pRb pathway and inducing a reversible senescence‑like state. From a translational perspective, such an outcome suggests the combination may suppress tumor cell growth temporarily but may not achieve durable eradication of LGSOC cells as monotherapy. The reversibility observed after drug removal raises considerations about potential tumor regrowth and the need for strategies that either convert transient arrest into irreversible cell death or eliminate arrested cells.
This work is presented as a preprint on bioRxiv and has not undergone peer review. The abstract provides primary outcomes and key molecular associations but does not include detailed experimental protocols, specific concentrations, exposure durations, numerical effect sizes, sample sizes, or statistical analyses in the summary text; those details would need to be obtained from the full manuscript or supplementary material. The study lists funding support from DxQuest Inc., North America, and the Gerald Bronfman Department of Pathology, McGill University.
Note: This summary and interpretation are restricted to findings reported in the source abstract and article metadata. Specific experimental parameters and quantitative data were not reported in the abstract and should be consulted in the full text or supplementary files for detailed evaluation.