Manuscript Animal Model - Value Rawdata

ABSTRACTBackgroundOvarian cancer (OC) is often diagnosed at advanced stages, leading to extensive peritoneal carcinomatosis (PC) and poor prognosis. Although intraperitoneal drug delivery systems (iDDS) are promising to target residual microscopic disease after cytoreductive surgery, reproducible and clinically relevant murine PC models remain limited. This study compared two OVCAR-3-based intraperitoneal engraftment strategies (diffuse vs. localized) and evaluated the effects of cell inoculum density and basement membrane extract (BME) supplementation to identify a more robust and reliable PC model.MethodsImmunodeficient female nu/nu mice were engrafted with luciferase-expressing human OVCAR-3 cells. In the localized implantation model, either 1×10⁶ or 4×10⁶ cells were implanted into the preperitoneal space behind the rectus abdominis to form localized tumors. Then, after evaluating the results, the 1×10⁶-cell group was additionally tested in the presence of basement membrane extract (BME). In the intraperitoneal dissemination model, 1×10⁶ cells were co-injected with BME to promote diffuse peritoneal spread. Tumor progression in both models was monitored weekly using bioluminescence imaging (BLI), and animals were sacrificed at predetermined time points for macroscopic, histological, and immunohistochemical analyses.ResultsIn the localized implantation model, no differences were detected between 1×10⁶ and 4×10⁶ cells; therefore, 1×10⁶ was selected for subsequent experiments. Although the addition of BME initially increased tumor volume and partially attenuated the decline in BLI signal previously observed, the signal still progressively decreased over time. Histological analysis revealed extracellular matrix remodeling, apoptosis, and tumor regression, indicating limited long-term tumor viability in this localized model.In contrast, the intraperitoneal injection model generated a clinically relevant pattern of peritoneal dissemination. After an initial decrease, BLI signals showed a sustained increase, and necropsy confirmed multiple tumor nodules along the intestinal serosa, mesentery stomach, liver, and omentum.ConclusionsThe intraperitoneal injection model with the addition of BME more accurately reproduced the progression and distribution of human PC, providing a refined model for the preclinical evaluation of localized iDDS.