【Animal Modeling】-Construction of Nude Mouse Model of Clear Cell Renal Carcinoma and Study on the Sensitivity of Targeted Drugs

  Objective To establish a tumor animal model with patient-derived clear cell renal cancer cells, to detect the sensitivity of ccRCC PDCs to molecularly targeted drugs, and to provide theoretical and experimental basis for clinical diagnosis and treatment.

  Methods Nude mice were subcutaneously inoculated with ccRCC PDCs to establish tumor models, and the molecular targeted drugs sunitinib, sorafenib, lenvatinib, regorafenib, apatinib and anlotinib were administered orally by gavage. The drug was used to determine the inhibitory effect of the drug on the subcutaneous tumorigenesis of ccRCC PDCs in nude mice. Cells and tumor tissue samples were collected, and quantitative PCR technology was used to detect molecular targeted drug targets (receptor tyrosine protein kinases such as VEGFR and protein kinases belonging to MAPK signaling pathways such as ERK and AKT) to determine the genetic inheritance of ccRCC PDCs during the experiment. Whether the background remains stable.

  Results Five strains of ccRCC PDCs were successfully obtained and the nude mice were inoculated with the above ccRCC PDCs to obtain a subcutaneous tumor model of renal cancer in nude mice. However, when PDCs cells were expanded by tumorigenesis in nude mice, the expression of molecularly targeted drugs in tumor tissues was relatively stable; the inhibitory effect of molecularly targeted drugs on subcutaneous tumorigenesis of ccRCC PDCs in nude mice was clearly different from individual patients. , Among the selected molecular targeted drugs, the anti-tumor activity of Lenvatinib is stronger than that of other molecular targeted drugs.

  Conclusion In this study, the patient-derived clear cell renal cancer cell line was used to successfully establish an animal model of renal cancer and detect the sensitivity of renal cancer cells to molecularly targeted drugs, which can provide theoretical and experimental basis for related clinical diagnosis and treatment.