A2780 Xenograft Model
Ovarian cancer is most common in women over 40. It is particularly dangerous because it often goes undetected until after it has metastasized, when it is most difficult to treat. Treatments for ovarian cancer can include chemotherapy and/or surgery. The A2780 cell line was established from an ovarian cancer patient who had not yet received treatment. The A2780 model has been used in many ovarian cancer research studies. A 2009 Cancer Therapy article (Duiker et al.) used the A2780 xenograft model to characterize rhTRAIL (recombinant human tumor necrosis factor-related apoptosis-inducing ligand) and its DR5-receptor binding variant, rhTRAIL-DR5. Results demonstrated that cisplatin treatment increased surface expression of DR5 and so combination treatment with rhTRAIL-DR5 was most potent in inducing apoptosis (caspase-3 activation, cell death). Piotrowska et al. (Biomedical Pharmacotherapy, 2014) characterized DMU-212, a mitochondrial-mediated apoptosis inducing anti-cancer agent that had previously only been studied in fibroblasts and breast cancer. Results demonstrated that in the A-2780 cell line and xenograft model, DMU-212 induces cytotoxic effects and lower tumor burden. Finally, Sui et al. (Drug Des Devel Ther.) published a 2015 study using the EGFR-overexpressing A2870 xenograft model to investigate the combination therapy of a PARP inhibitor (olaparib aka AZD2281) with erlotinib. Results demonstrated a synergistic effect with erlotinib and olaparib on inducing autophagy and reducing phosphorylation of AKT and ERK1/2. The A2780 cell line is used to create the CDX (Cell Line Derived Xenograft) A2780 xenograft mouse model. The A2780 xenograft model has been used to characterize various aspects of ovarian cancer (neovascularization, Snail, Slug, cisplatin resistance, NMDA receptors, tinzaparin).
Basic Study Design
- A2780 cells are maintained in exponential growth phase under aseptic conditions.
- Cells are trypsinized and cell count viability is determined using a trypan blue exclusion assay (98% of cell viability is required). A2780 cell suspension is adjusted to appropriate density.
- Each mouse is singly subcutaneously injected into the right flank with 106 cells in 100 µL of a Matrigel- A2780 cell suspension.
- The injection sites are palpated up to three times weekly until tumors are established to an average size of 50-150 mm3 as measured via digital calipers.
- Animals are randomized into treatment groups. Administration of test compound is performed according to the pre-established treatment schedule.
- Mice weights are measured and recorded 3 times weekly; tumors are measured and recorded daily.
- End of study is reached when tumor size reaches 2,000 mm3 or the predetermined size limit per approved IACUC protocol.
- 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.