Establishment of a clear-cell renal cancer cell tumor xenograft model using patient-derived cells to examine cell sensitivity to molecular-targeting agents
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1.Department of Urology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, China. 2. Department of Urology, Navy 971 Hospital of the Chinese People’s Liberation Army, Qingdao 266071. 3. Fifth Medical Center, General Hospital of Chinese People’s Liberation Army Clinical Research Management Center, Beijing 100039. 4. Department of Urology, First Medical Center, General Hospital of Chinese People’s Liberation Army, Beijing 100853

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R-33

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    Abstract:

    Objective To examine the sensitivity of clear-cell renal carcinoma cells ( ccRCCs) using patients- derived cells (PDCs) to molecular-targeted drugs in patient-derived tumor xenograft (PDX) models.Method PDCs from ccRCCs were subcutaneously inoculated into nude mice to establish a tumor model. The molecular-targeting drugs, sunitinib, sorafenib, lenvatinib, regorafenib, apatinib and anlotinib, were orally administered to examine the inhibitory effect of the drug on the subcutaneous formation of PDC-derived ccRCCs in nude mice.Cell and tumor tissue samples were analyzed via qPCR. The targets of the molecular-targeting drugs (i.e., receptor tyrosine protein kinases, such as VEGFR, and protein kinases of the MAPK signaling pathway such as ERK and AKT) were examined.Result Five lines of PDC- derived ccRCCs were successfully established, and the nude mice were injected with PDC-derived ccRCC to obtain a subcutaneous tumor model of kidney cancer in nude mice. Expression of the target molecules of these drugs decreased during in vitro PDC culturing. Moreover, expansion of these molecules in the tumor tissues was relatively stable. The inhibitory rates of the molecular-targeting agents differed for each drug, and the antitumor activity of lenvatinib was stronger than that of several of the other drugs.Conclusions PDC-derived ccRCCs can be used to establish a mouse model of kidney cancer and test the sensitivity of renal cancer cells to molecular-targeted drugs. These models can provide a rational and experimental basis for relevant clinical diagnosis and treatment.

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History
  • Received:December 02,2019
  • Revised:
  • Adopted:
  • Online: July 23,2020
  • Published: