Publication Date:
2016-05-13
Description:
ABSTRACT We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease. Human MKN45 poorly differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination-based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra-peritoneal tumors and ascites contained mostly quiescent G 1 /G o cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors still formed in the peritoneal cavity in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium with cancer cells mostly in G 0 /G 1 , visualized by FUCCI imaging. In contrast, OBP-301 telomerase-dependent adenovirus treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G 2 phases in the early-stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP-301 significantly reduced the size of tumors (p 〈 0.01) and ascites even in a late-stage carcinomatosis peritonitis model. These data suggest that quiescent peritoneally-disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP-301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. This article is protected by copyright. All rights reserved
Electronic ISSN:
0091-7419
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
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