Figure 8.
Effects of ET receptor antagonists on ET-1-induced proliferation in vitro and tumor growth in vivo. A: 100 nmol/L of ET-1 was added to quiescent KS IMM cells. ABT-627, the ETAR antagonist (1 μmol/L), A-192621, the ETBR antagonist (1 μmol/L) and A-182086, the ETA/BR antagonist (1 μmol/L), were incubated 15 minutes before the addition of ET-1. [3H]thymidine incorporation was analyzed 24 hours after the addition of the agonist. Data are means of results from three experiments each performed in sextuplicate. a, P ≤ 0.001 compared to control. b, P ≤ 0.01 compared to ET-1 100 nmol/L. c, P ≤ 0.001 compared to ET-1 100 nmol/L. B: Antitumor activity of ET receptor antagonist treatment on established KS IMM human xenografts. Mice were injected s.c. with 3 × 106 KS IMM cells. After 7 days the mice were treated i.p. for 21 days with vehicle, with ABT-627 (2 mg/kg/day), with A-192621 (10 mg/kg/day), or with A-182086 (2 mg/kg/day) i.p. on days 1 to 21, 7 days after tumor implant. Three different experiments with a total of 40 mice for each experiment were performed. In each experiment, each group consisted of 10 mice. Data represent the averages; bars ± SD *, P ≤ 0.02; **, P ≤ 0.001 compared with control.