An in vivo human tumor xenograft model of etoposide resistance.

HCT-116 and HCT-116/E represent human colon carcinoma lines characterized in vitro as sensitive and resistant, respectively, to etoposide. Using both subrenal capsule (src) and sc implants, we sought to develop in vivo tumor models of these cell lines. Src implantation of tumor fragments into athymic mice yielded reproducible growth (165-271%) for both tumor models during the 10-day assay period. The maximum therapeutic effects for etoposide on the preferred schedule (Days 1 and 5, ip) were (mean +/- SD) 78% +/- 10% tumor inhibition versus src HCT-116 compared to 45% +/- 14% tumor inhibition versus src HCT-116/E (p less than 0.001). The modest but significant differential sensitivity toward etoposide seen in the src tumor setting was not observed in the sc tumor models. Principally, this was due to the insensitivity of sc HCT-116 to etoposide, even when treatment was initiated one day post-implant. Interestingly, mitomycin C, included as a positive reference drug, was more active versus sc HCT-116/E than sc HCT-116. In summary, src tumor models for etoposide sensitivity and resistance have been developed as in vivo counterparts for cell lines with characterized differential sensitivity to etoposide in vitro.