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An MMP13-Selective Inhibitor Delays Primary Tumor Growth and the Onset of Tumor-Associated Osteolytic Lesions in Experimental Models of Breast Cancer

Figure 5

Metastatic burden in the lungs (A) and brain (B) of mice treated with vehicle or Cmpd-1 (low or two-tier regimens) following intra-cardiac inoculation of MDA-MB-231 cells, as assessed by qPCR for the human Alu repeat sequence on DNA extracted from whole organs.

Mouse only controls were included in the qPCR analysis and all mouse only samples were negative for human DNA. Mean values are indicated. (C) Percentage survival of intra-cardially inoculated mice. Cmpd-1 did not prolong overall survival of the mice treated with Cmpd-1 (Kaplan-Meier survival). (D) Metastatic burden in the lungs of mice treated with vehicle or Cmpd-1 (low or two-tier regimens) following mammary fat pad inoculation of spontaneously metastasizing 4T1.2 cells. Tumor burden in lungs was assessed by luminescence intensity of ex-vivo lung imaging using IVIS at the termination of the experiment. Cmpd-1 showed no inhibitory effect on metastatic tumor burden on soft tissues in both xenograft and syngeneic mice models (Mann-Whitney test). (E) Representative images of lung macrometastasis in mice inoculated with 4T1.2-Luc and treated placebo/low dose/high dose.

Figure 5

doi: https://doi.org/10.1371/journal.pone.0029615.g005