Toxicity and antitumor response following ProVP16-II therapy in mice. A/J mice (n = 6) were injected intraperioteoneally with ProVP16-II (20 and 60 mg/kg) and VP16 (20 mg/kg) on days 1, 3, 5, 7, 9, and 11 and with VP16 (60 mg/kg) on days 1, 3, and 5 (A). The body weight was determined for each animal over time and calculated as percent of total weight observed on day 0. An event as indicated by Kaplan-Meier plots is defined by loss of body weight of more than 20%. The antitumor effect of ProVP16-II therapy was determined in a multidrug-resistant xenograft model (B-C). SCID mice (n = 7) were injected subcutaneously with 5 × 10⁶ MOVP-3 cells, and primary tumors of 250 mm³ average size were established 55 days after inoculation. Treatment consisted of intraperitoneal injections with ProVP16-II (45 and 15 mg/kg), VP16 (15 mg/kg), and solvent on days 55, 57, 59, 69, 71, 87, and 90 after tumor cell inoculation. Tumor growth was monitored by microcaliper measurements and tumor size was calculated as described in “Materials and methods” (B). Differential findings between experimental groups of animals treated with ProVP16-II (45 and 15 mg/kg) and control groups (solvent and VP16) were statistically significant (P < .001 after day 63) (B). The body weight of treated animals was determined over time and calculated as percent of body weight on day 57 (C). At the end of the treatment experiment, remaining subcutaneous tumors were removed and analyzed by RT-PCR for gene expression of MDR-1 except from mice treated with 45 mg/kg with no residual tumor. Representative signals of one tumor of each group is depicted and compared with MDR-1—expressing VCR-100 cells used as a positive control. The presence of 229- or 127-bp signals indicate expression of MDR-1.