Figure 4.

Cathepsin inhibition sensitizes tumors to Taxol treatment. (A) Trial schematic showing dosing of MTD Taxol, JPM, and CLD Cyclo in the 5-wk regression trial (from 9–14 wk of age). (B) Tumor volume curves for PyMT transgenic mice treated with Taxol, JPM, and Taxol+JPM, compared with vehicle, based on twice-weekly external palpation caliper measurements. n = 17 vehicle, 16 JPM, 16 Taxol, 16 Taxol+JPM. P-values in B–D derive from area-under-the-curve (AUC) analyses, with pairwise comparisons between indicated groups, although some of these effects did not reach statistical significance when adjusted for multiple comparisons. (C) Tumor volume curves for Cyclo- and Cyclo+JPM-treated mice compared with vehicle-treated mice. n = 14 Cyclo, 14 Cyclo+JPM. (D) Tumor volume curves for Taxol+Cyclo- and Triple-treated mice compared with vehicle-treated mice. n = 16 Taxol+Cyclo, 16 Triple. (E) End-stage tumor volumes based on measurements of excised tumors. (*) P < 0.05, (**) P < 0.01, (***) P < 0.0001, unpaired t-tests. Comparisons are with the vehicle group unless otherwise indicated. n = 14–15 per treatment group.