HK Inhibits Angiogenesis/Peritoneal Dissemination Figure 2. Effect of honokiol on metastasis of gastric tumor cells in vivo. [18F]-FDG-PET served as a surrogate measure of therapeutic efficacy. Tumors in nude mice were established for 7 days after the intraperitoneal inoculation of gastric cancer cells (MKN45, A; SCM-1, B). Mice were then injected intraperitoneally with honokiol (5 mg/kg/twice per week). Twenty-eight days after honokiol treatment, FDG-PET/CT images of mice were taken, and then mice were sacrificed for macroscopic examination of the distribution of disseminated metastasis. Representative FDG-PET/CT images of animals inoculated with MKN45 (A-a) or SCM-1 (B-a) gastric cancer cells with or without honokiol (HK) treatment are shown. HK (5 mg/kg) was administered by intraperitoneal injection. The maximum intensity projection of typical representative nude mice (left, tumor control; right, HK treatment) is shown. Moreover, many metastatic nodules were found in the mesentery of the control mice inoculated with MKN45 (A-b) or SCM-1 (B- b) cells. In contrast, peritoneal metastasis was observed sporadically in honokiol-treated mice. doi:10.1371/journal.pone.0043711.g002 Image-Pro Plus software is shown in Figure 7. The results of analysis with confocal microscope also showed that honokiol abolished the tyrosine (Tyr705) phosphorylation of STAT-3 in AGS cells and HUVECs (Fig. 8A). We further examined the STAT-3 phosphorylation in peritoneal metastatic tumors isolated from nude mice inoculated with MKN45 cells with or without honokiol (5 mg/kg) treatment. Immunohistochemical analysis showed that p- PLOS ONE | www.plosone.org 4 August 2012 | Volume 7 | Issue 8 | e43711