title: ZnPPIX inhibits peritoneal metastasis of gastric cancer via its antiangiogenic activity.
abstract: Our previous study suggests that heme oxygenase-1 (HO-1) may play an important role in the metastasis of gastric cancer. Zinc protoporphyrin IX (ZnPPIX) is a special HO-1 inhibitor that inhibits the angiogenesis of pancreatic and lung cancer. In this study, we employed ZnPPIX to investigate the role of HO-1 in peritoneal metastasis of gastric cancer (PMGC) and explored the potential mechanism. We established animal model of PMGC by orthotopic implantation into nude mice of human gastric cancer cell line GC9811-P with high peritoneal metastasis potential. The mice were injected intraperitoneally with saline, CTX or ZnPPIX. Tumor microvessel density (MVD) in peritoneal metastatic nodules was determined by immunohistochemistry, and vascular endothelial growth factor (VEGF) level was determined by ELISA. We found that the number, volume, weight of peritoneal metastatic nodules and volume of seroperitoneum in ZnPPIX (4 mg/kg) group decreased remarkably compared with control group. MVD value and VEGF level of peritoneal metastatic tumor in ZnPPIX (4 mg/kg) group also decreased significantly, while the survival rate and survival time of the mice were higher than control group. ZnPPIX dose-dependently suppressed VEGF and GC9811-P induced angiogenesis. Furthermore, ZnPPIX suppressed VEGF induced reactive oxygen species production and ERK phosphorylation in human umbilical vein endothelial cells. In conclusion, our results suggest that HO-1 plays an important role in PMGC and ZnPPIX is an effective antitumor and antiangiogenic agent for PMGC.
authors.affiliation: Department of Intensive Care Unit, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
authors.forename: Fu-tai
authors.initials: FT
authors.lastname: Shang
authors.affiliation: Department of Intensive Care Unit, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China. Electronic address: huiliangliang@163.com.
authors.forename: Liang-liang
authors.initials: LL
authors.lastname: Hui
authors.affiliation: Department of Intensive Care Unit, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
authors.forename: Xu-sheng
authors.initials: XS
authors.lastname: An
authors.affiliation: Department of Intensive Care Unit, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
authors.forename: Xiang-cheng
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: Department of Intensive Care Unit, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
authors.forename: Shi-guang
authors.initials: SG
authors.lastname: Guo
authors.affiliation: Department of Intensive Care Unit, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
authors.forename: Zang
authors.initials: Z
authors.lastname: Kui
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D010766:Phosphorylation / Q000187:drug effects; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C017803:zinc protoporphyrin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Angiogenesis; Heme oxygenase-1; Peritoneal metastasis of gastric cancer; VEGF; ZnPPIX