Abstract
We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. 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 G1/Go cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G0/G1, visualized by FUCCI red. In contrast, OBP-301 telomerase-dependent adenovirus-treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G2 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 results 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. J. Cell. Biochem. 118: 3635–3642, 2017.
Original language | English |
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Pages (from-to) | 3635-3642 |
Number of pages | 8 |
Journal | Journal of Cellular Biochemistry |
Volume | 118 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2017 |
Keywords
- ADENOVIRUS
- CARCINOMATOSIS PERITONITIS
- CELL CYCLE
- CISPLATINUM
- FUCCI
- GASTRIC CANCER
- IMAGING
- NUDE MICE
- ORTHOTOPIC
- PACLITAXEL
- TELOMERASE
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology