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. 2017 May 15;7:94. doi: 10.3389/fonc.2017.00094

Figure 4.

Figure 4

Effects of ENMD-2076 treatment on SA-β-Gal, p16, p53, and p73 expression in PDX models exhibiting initial sensitivity to ENMD-2076 treatment and at the time of acquired resistance. (A,B) Senescence and IF analysis of tumors harvested from CU_TNBC_002 and CU_TNBC_005 treated with vehicle control, ENMD-2076 treated at day 30 (sensitive), and ENMD-2076 treated at the time of acquired resistance. Acquired resistance was defined as a doubling in tumor volume from day 30 while receiving ENMD-2076 treatment. ENMD-2076 treatment was administered at 200 mg/kg once daily by oral gavage. Representative images for SA-β-gal expression were acquired using a Zeiss microscope at 40× magnification. Scale = 5μm. Note the presence of blue SA-β-gal staining in both models at the time of acquired resistance. Representative immunofluorescence (IF) images were acquired using confocal microscopy at 60× magnification. Scale = 5μm. (C,D) Quantification of mean pixel intensity of the IF analysis. Sensitive tumor pixel intensity was compared to vehicle control and acquired resistance pixel intensity was compared to the sensitive tumor. **p < 0.01, ***p < 0.001, ****p < 0.0001.