【Animal Modeling】-Nude mouse model of clear cell renal cancer

  Objective: To establish a patient-derived tumor xenograft model (PDX model) of patient-derived clear cell renal cell carcinoma (patient-derived cells, PDC), detect the sensitivity of ccRCCPDC to molecularly targeted drugs, and provide a clinical diagnosis And treatment theory and experimental basis.

   Method: Inject ccRCCPDC subcutaneously into nude mice, and give the nude mice orally the molecular targeted drugs snitinib (snitinib), sorafenib (sorafenib), lebatinib (lembatinib), legorafenib (legorafenib), apatinib and anrotinib. The inhibitory effect of the drug on the formation of ccRCCPDC subcutaneous tumors was measured. Collect cell and tumor tissue samples, and use quantitative PCR technology to detect molecular targeted drug targets (VEGFR and other receptor tyrosine protein kinases and other protein kinases belonging to the ERK, AKT and MAPK signaling pathways). And determine the genetic background of ccRCCPDC during the experiment.

  Result: We successfully obtained 5 strains of ccRCCPDC, inoculated the above-mentioned ccRCCPDC into nude mice, and obtained a nude mouse subcutaneous tumor model of kidney cancer. In the process of culturing PDC cells in vitro, the expression of molecular target drug targets etc. decreases or disappears. However, due to tumorigenesis in nude mice, the expression of molecular target drug targets in tumor tissues is relatively stable through the expansion of PDC cells. The inhibitory effect of molecularly targeted drugs on subcutaneous tumors of nude mice ccRCCPDC varies from patient to patient. Among the selected molecular target drugs, lombartinib has stronger anti-tumor activity than some other molecular target drugs.

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