Substance P Receptor Signaling Mediates Doxorubicin-Induced Cardiomyocyte Apoptosis and Triple-Negative Breast Cancer Chemoresistance

Figure 2

Effect of substance P receptor antagonist pretreatment on doxorubicin-induced apoptosis of cardiomyocytes and triple-negative breast cancer cells. Levels of apoptosis as determined by the TUNEL assay, in response to DOX in aprepitant pretreated versus untreated rat H9C2 cardiomyocytes and MDA-MB 231 TNBC cells. A photomicrograph of H9C2 cells from (a) control aprepitant treated, (b) DOX-treated, and (c) DOX + aprepitant pretreated cells showing numerous strongly positive brown apoptotic nuclei in the DOX group and very few faintly positive nuclei in the DOX + aprepitant group (arrows depict positive cells, original magnification 200x). (d) Number of apoptotic H9C2 cells in the 2 experimental groups and all control groups (media, vehicle, and aprepitant alone groups, all showing no positive apoptotic cells) (, ANOVA, ). Only statistical comparisons between DOX and DOX + AP are shown. A photomicrograph of MBA-MD 231 cells from (e) control aprepitant treated, (f) DOX-treated, and (g) DOX + aprepitant pretreated cells showing numerous strongly positive brown apoptotic nuclei in the DOX + aprepitant group versus the group treated with DOX alone (arrows depict positive cells, original magnification 200x). (h) Number of apoptotic MBA-MD 231 cells in the 2 experimental groups and all control groups (media, vehicle, and aprepitant alone groups, all showing no positive apoptotic cells) (, ANOVA, ). Only statistical comparisons between DOX and DOX + AP are shown.

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