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. 2015 Feb 20;107(4):djv017. doi: 10.1093/jnci/djv017

Figure 6.

Figure 6.

The effect of anti-MMP14, radiation, and their combination on BC models. A-D) The combination of DX-2400 and radiation is modestly synergistic in the 4T1 tumor model and additive in the E0771 tumor model. Tumor growth curves for 4T1 tumors (A) and E0771tumors (C) in mice treated with control (CT), DX-2400 (DX), local fractionated irradiation (R; days 4, 5, and 6), or their combination (DXRDX). Mice were maintained and tumors measured until tumors reached approximately 1000mm3 or until morbidity was evident. Data are presented as median and interquartile range (panels A and C) with individual curves presented in Supplementary Figure 11 (available online). All other data are presented as median with the interquartile range (box) and maximum and minimum values (whiskers). Sample size: n = 6 for 4T1 and n = 4 or 5 for E0771. The time (days) taken for tumors to grow to 800mm3 was used to assess tumor growth delay (panels B, 4T1, and D, E0771). The combination of DX-2400 and radiation was synergistic in the 4T1 model (B; expected additive range of DX+R is shown as horizontal dashed lines), while the combination was additive in the E0771 model (D). E) The effects of the timing of MMP14 inhibition. Ten DX-2400 injections (DXRDX) compared with three initial injections of DX-2400 (DXR; DX on days 0, 2, and 4 with radiation on days 4, 5, and 6) and seven postirradiation injections (RDX). F) The effects of iNOS were assessed using 1400W in addition to DX (DXW), radiation (RW), and the combination (DXRDXW). The synergy associated with combination treatment in the 4T1 model was lost when iNOS was inhibited. Analysis of variance with Bonferroni post hoc t test was performed for analysis of tumor growth. All statistical tests were two-sided. Additional data are provided in Supplementary Figure 11 (available online). CT = control; DX = DX-2400; DXR = three initial injections of DX-2400 plus radiation; DXRDX = ten DX-2400 injections plus radiation; DXRDXW = combination DXRDX plus 1400W; DXW = DX-2400 plus 1400W; RDX = radiation followed by DX-2400; RW = radiation plus 1400W.