Figure 5

(A) RB242 is more potent than RB200 in inhibition of proliferation of cultured tumor cells. (Top panels) Serum-starved BxPC3 pancreatic cancer cells were treated with 3 nM of either TGF-α (top left) or NRG1-β (top right) for 3 d in the presence of increasing concentrations of RB200 or RB242. (Bottom left) Serum-starved MCF7 cells were treated with 3 nM of NRG1-β for 3 d in the presence of increasing concentrations of RB200 or RB242. (Bottom right) Proliferation of H1437 NSCLC cells in growth medium (RPMI1640/10%FBS) for 5 d in the presence of increasing concentrations of RB200 or RB242. Cell proliferation was quantified as described in Methods. Results are means ± SEM of 8 or 16 replicates. Approximate EC₅₀ values for BxPc3 cells were determined with the constraint type set to top constant equal to 100. (B) RB242 has improved anti-tumor activity in a mouse tumor xenograft model. Nude mice were transplanted with H1437 NSCLC cells subcutaneously as described in Methods. When the tumor volume reached approximately 100 mm³, the mice were treated with either PBS vehicle (◯) or RB200 (▼) or RB242 (▲) at 12 mg per Kg administered intra-peritoneally three times weekly for 3 wks. There were nine mice per each treatment group. Data are expressed as mean tumor volume ± SEM. ** = P < 0.01 by two-way ANOVA with Bonferroni’s post test.