Figure 5. Notch and Hedgehog Inhibition Abrogates the Acquisition of Docetaxel Resistance.

(A) Changes in tumor volume of DU145 and 22RV1 xenografts treated with Dexamethasone alone, double combinations, triple combinations, and quadruple combination. Dose schedules were Dexamethasone (15 mg/kg/i.p. daily), Docetaxel (10 mg/kg/i.p. once a week for 3 weeks every 4 weeks), DBZ (10 mM/kg/ip daily for 15 days every 4 weeks), and Cyclopamine (50 μg/kg/sc daily).
(B) Quantitative RT-PCR of Notch and Hedgehog target genes in DU145 and 22RV1 xenografts obtained from mice treated with the same drugs and concentrations as in (A). Bars represent fold change in mRNA levels relative to vehicle (control).
(C) Microphotographs illustrate the expression of low molecular weight cytokeratins (CK18 and CK19) in DU145 and 22RV1 prostate cancer tumor xenografts in NOD/SCID mice treated for 4 weeks with the same drugs as in (A). Magnifications illustrate CK− cells. Histogram represents the percentage of CK− cells detected in DU145 and 22RV1 xenografts for each treatment arm. Four xenografts for each treatment group where analyzed. Data is represented as means ± SD. *p < 0.05.
See also Figure S5.