Oncopig Hepatocellular Carcinoma Cell Lines Recapitulate Human Liver Cancer Chemotherapy Responses

M.F. Neto, H.H. Chen, J. Newson, K.M. Schachtschneider, R.C. Gaba
UIC College of Medicine Research Forum, December 2017, Chicago, IL
The Oncopig Cancer Model (OCM) is a novel transgenic swine platform that recapitulates human malignancy through development of site/cell specific tumors after Cre recombinase-induced expression of KRAS G12D and TP53 R167H transgenes. Given similar drug metabolism between humans and pigs, the OCM could address unmet clinical needs by facilitating translation of results obtained in preclinical murine studies to human clinical pra ctice, which is critical given that many therapeutics showing promise in mouse studies fail in clinical trials. In order to investigate the prognostic capabilities of the OCM for drug screening, we tested the hypothesis that Oncopig and human hepatocellular carcinoma (HCC) exhibit similar responses to commonly used chemotherapy agents. Responses to four clinically employed cytostatic (sorafenib) and cytotoxic (doxorubicin, cisplatin, mitomycin C) HCC chemotherapeutics were compared between Oncopig and three representative human HCC cell lines (SNU-387, SNU-475, HepG2). Results of MTT time course assays (triplicate performance) revealed that Oncopig and human HCC cell lines display similar sensitivities to all four chemotherapeutics when administered at comparable, clinically relevant concentrations. These results indicate that the Oncopig represents a valuable tool for screening promising chemotherapy agents, providing a novel large animal bridge between preclinical investigation in small animal models and human clinical trials.