Figure 1
In vivo chemoresistance. (A) Subcutaneous human HUH-7 tumors were established in SCID mice by injection of 5×106 HUH-7 cells into the flanks of animals (n=6). CPA treatment was started on day 12 after tumor implantation with 75 mg/kg CPA every sixth days. Metronomically scheduled CPA treatment resulted in significant tumor growth delay. Tumor volume of treated mice was constant up to day 75 after tumor cell implantation, whereas tumors in the control group exhibited a tumor volume doubling time of 2.5 days. Around day 75 after tumor cell implantation tumor volume began to increase in the CPA treated group, despite ongoing treatment with a tumor doubling time of 3.5 days. (B) Cells isolated from resistant CPA treated tumors (HUH-REISO) were cultured in vitro and, after several passages, reimplanted in SCID mice (n=6) again, with CPA therapy (75mg/kg every sixth days) starting at day 10 after cell implantation. A cell line established from in vivo passaged tumor cells (HUH-PAS) served as control. Tumors derived from HUH-REISO cells revealed a tumor volume doubling time (under therapy) of 4.5 days, whereas tumor growth in the control group was not evident within the observed time.