Figure 4. Pharmacodynamic analysis of CPX showed suppression of survivin levels in tumor of human pancreatic xenograft mice as well as inhibition of tumor growth, in a concetration- and time-dependent manner.

Female SCID mice were inoculated subcutaneously with BxPC-3 (3 × 10⁶ cells/mouse) or PANC- 1 (3 × 10⁶ cells/mouse) or MIA PaCa-2 (3 × 10⁶ cells/mouse) tumor cells. When local tumors were established, mice were randomly subdivided into groups after daily single oral gavage of CPX at concentration 5 mg/kg, 15 mg/kg, and 25mg/kg. Tumor tissues were resected on 0, 5th, 15th, 30th day after the daily administration of CPX. Tumor tissues were also resected on day 35^th day (5 days after stopping the administration of CPX). (A) The tumor volumes within each cell line group were calculated (thrice/per week) after oral gavage of CPX at 5, 15 and 25 mg/kg daily. The mean ± SD (n = 6) data on tumor volumes are presented in the indicated graph ^*Significant difference (P < 0.05), ^**Significant difference (P < 0.01) versus controls (untreated) per time point. (B) Western blot analysis was followed for detecting survivin protein levels in tumor tissues (upper panel). The densitometric quantification of survivin reflects average values ± SD (n = 3) of at least 3 independent experiments. ^*p < 0.05 ^**P < 0.01 ^***P < 0.001 vs. Control group of the indicated time point (lower panel). (C) Survivin levels as measured by ELISA after increasing doses of CPX at 5, 15, 25 mg/kg (n = 3 per time point). Survivin reflects average values ± SEM of at least 3 independent experiments. ^*p < 0.05 ^**P < 0.01 ^***P < 0.001 vs. Control group of the indicated time point.