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Peripheral Opioid Antagonist Enhances the Effect of Anti-Tumor Drug by Blocking a Cell Growth-Suppressive Pathway In Vivo

Fig 4

Mouse models of intraperitoneal low-dose Doc therapy corresponding to 3 different phases (early, middle, and late) in the progression of peritoneal dissemination.

Survival curves for the early phase (A), middle phase (B), and late phase (C) of a peritoneal metastasis model. Administration of Doc (0.5 mg/kg) was started 1 day (A), 7 days (B) or 14 days (C) after the inoculation of 60As6-Luc cells, and was continued until the endpoint criteria were reached (n = 5, *p<0.05, vs. saline). D, representative histological image (hematoxylin-eosin, HE) and Ki-67 immunostaining of 60As6 xenograft. Scale bar, 50 μm. E, detection of the progression of peritoneal dissemination in real-time using an in vivo photon-counting analysis of mice treated with saline, Doc or Doc/MNTX (0.3 mg/kg). Beginning on day 7 after inoculation, the mice were divided into 4 groups based on photon counts. The mice were then treated intraperitoneally with the above reagents twice weekly until the endpoint criteria were met (middle phase).

Fig 4

doi: https://doi.org/10.1371/journal.pone.0123407.g004