Figure 6
Synergy in OE-19 cells was associated with a combination-induced decrease in pERK and tumor growth inhibition in vivo. (a) OE-19 and NCI-N87 cells were treated with DIACC3010 and/or trastuzumab and total cellular lysates were immunoblotted, as indicated on the left. Black-edged rectangles delineate the blot. This western blot analysis revealed that OE-19 cells, which had a synergistic response to the DIACC3010 + trastuzumab combination, had a decrease in pERK/ERK following treatment with trastuzumab, either alone or combined with DIACC3010. NCI-N87 cells, which did not respond synergistically to the combination, had an increase in pERK/ERK following treatment with both monotherapies and a further increase in response to the combination. (b) Mice were injected subcutaneously in the flank with 1 × 107 OE-19 cells. Once tumors reached approximately 200 mm3, mice were assigned to treatments (n = 6): vehicle, DIACC3010 at 30 mg/kg orally/daily (po, QD), trastuzumab 15 mg/kg once per week (iv, QW). The monotherapy treatments were not effective (p > 0.05), whereas the combination significantly inhibited tumor growth (*p < 0.01). Original blots are presented in Supplementary Fig. 9.
