RXF393 Xenograft Model

RXF393 Xenograft Model

Kidney, or renal, cancer often occur as RCC (renal cell carcinoma) or TCC (transitional cell carcinoma) in two main locations: the renal pelvis or the renal tubule. Renal cancer most commonly is seen in those over 60 years of age. Risk factors include tobacco smoking and obesity. Roughly 200k new cases of renal cancer are seen each year in the U.S. The RXF393 cell line was taken from a 53 year old male patient with renal cancer. The RXF-393 model has been used in many pancreatic cancer research studies and is part of the NCI-60 screen. A 2017 PNAS article (Bouvard et al.) used the RXF393 cell line, among others, to investigate the small molecule stauprimide, an analog of staurosporine and promoter of embryonic stem cell differentiation. Stauprimide has been shown to down-regulate and suppress MYC transcription in these cancer cells and cause inhibition of xenograft tumor growth. Pretto et al. used the RXF393 cell line in a 2015 Oncotarget article to investigate the mechanism of sunitinib, an anti-angiogenic agent. Data demonstrated that sunitinib has an anti-cachectic effect, preventing muscle wasting and body weight loss, overall increasing mouse survival. This suggests the use of STAT3-targeting antiangiogenic agents for cachexia patients. Finally, a 1997 Cancer Research article (Kadhim et al.) used the RXF393 cell line to study BCH-4556, an anticancer nucleoside analog also known as beta-L-dioxolane-cytidine. The group validated the compound efficacy in xenograft models and observed tumor regression, supporting its further study in clinical trials. BCH-4556 is now known as troxacitabine. The RXF393 cell line is used to create the CDX (Cell Line Derived Xenograft) RXF393 xenograft mouse model. The RXF393 xenograft model has been used to study pancreatic cancer treatments (lapatinib, S-1, small molecule inhibitors, immunotherapies, etc.).

Basic Study Design

  1. RXF393 cells are maintained in exponential growth phase under aseptic conditions.
  2. Cells are trypsinized and cell count viability is determined using a trypan blue exclusion assay (98%-99% of cell viability is required).  RXF393 cell suspension is adjusted to appropriate density.
  3. Each mouse is singly subcutaneously injected into the right flank with 106 – 107 cells in 150-200 µL of a Matrigel-RXF393 cell suspension.
  4. The injection sites are palpated up to three times weekly until tumors are established to an average size of 80-120 mm3 (measured via digital calipers).
  5. Animals are randomized into treatment groups. Administration of test compound is performed according to the pre-established treatment schedule.
  6. Mice weights are measured and recorded 2-3 times weekly; tumors are measured and recorded daily.
  7. End of study is reached when tumor size reaches 2,000 mm3 or the predetermined size limit per approved IACUC protocol.
  8. Final necropsy and tissue collections are performed for appropriate downstream analysis. Tumors are excised, weighed and documented by digital imaging. Tumors and tissues can be stabilized in RNAlater, snap frozen in LN2 or prepared for histology.