Purpose To explore the feasibility of Diannan miniature pigs as a xenograft model for colorectal cancer (CRC) and evaluate the impact of immunosuppressive regimens on early tumor growth and host physiological functions, optimizing large-animal CRC models.
Methods HT-29 tumor tissue blocks derived from nude mice were surgically transplanted into the subcutaneous tissue of the lateral abdomen of Diannan miniature pigs. Cyclosporine was administered intravenously (15 mg/kg) from 0 to 7 d post-surgery, followed by intramuscular injection (5 mg/kg) from 8 to 42 d. Tumor volume, cyclosporine blood concentrations, blood physiological and biochemical indicators of transplanted sites in recipient pigs were dynamically monitored. Additionally, HE staining was performed at the experimental endpoint to assess tissue pathology.
Results Transient tumor enlargement was observed initially (0-10 d), but the graft gradually regressed and completely disappeared by 18-47 d due to significant cyclosporine concentration fluctuations (59.3-291.52 nmol/L) and ineffective immunosuppression, leaving only lymphocyte infiltration. Hematological disturbances were evident, including a 19.00% decrease in hemoglobin, 28.10% reduction in white blood cell count, and a 134.00% surge in neutrophil count. Hepatic impairment was observed, presenting with elevated alanine amino-transferase and aspartate transferase, and reduced total protein and albumin, while renal function remained unaffected.
Conclusion The Diannan miniature pig CRC xenograft model failed to support long-term tumor survival due to unstable immunosuppression and microenvironmental incompatibility, yet it revealed critical interactions between immune regulation and host metabolic responses. Future studies should prioritize the optimization of combination immunosuppressive regimens and orthotopic transplantation strategies to advance the application of large-animal models in CRC research.
DownLoad: