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Liu W.,Suzhou University | Liu W.,Soochow University of China | Liu W.,Chinese Institute of Materia Medica | Liu W.,Key Laboratory of Thrombosis and Hemostasis | And 32 more authors.
Toxicology and Applied Pharmacology | Year: 2015

Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. © 2015 Elsevier Inc.


Bu Z.,Soochow University of China | Bu Z.,Key Laboratory of Thrombosis and Hemostasis | Pan Y.,Soochow University of China | Pan Y.,Key Laboratory of Thrombosis and Hemostasis | And 8 more authors.
Hybridoma | Year: 2012

In this study, using an in vitro tube formation model, we observed that SZ117, a monoclonal antibody against matrix metalloproteinase-2 (MMP2), attenuated a capillary-like tube structure formed by tumor endothelial cell 3B11 and human sarcoma cell MG63. In addition, gelatin zymography showed that SZ117 markedly inhibited MMP2 activity, but did not affect the capability of MMP9-mediated gelatin degradation. These data suggest that SZ117 might have an anti-tumor angiogenic effect and that angiogenic tumor cells and MMP2 may be targeted by monoclonal antibodies for novel anti-tumor angiogenic and anti-cancerous drug discovery. © 2012, Mary Ann Liebert, Inc.


Zhang G.,Soochow University of China | Shang B.,Soochow University of China | Shang B.,Key Laboratory of Thrombosis and Hemostasis | Yang P.,Soochow University of China | And 7 more authors.
Stem Cells and Development | Year: 2012

Induced pluripotent stem cells (iPSCs) have recently boomed enthusiasm in stem cell therapy, whereas high potential tumorigenesis of iPSCs has become the biggest obstacle for clinic application and the tumorigenic genes in iPSCs have not been well documented. In this investigation, using tools of bioinformatics, we analyzed the all available datasets regarded to iPSCs from 11 differentiated cell lines and revealed 593 iPSC consensus genes. Notably, of the 593 genes, 209 were expressed in human tumor cell lines and cancer tissues, and some of them were expressed in the iPSC-differentiated hepatocytes; remarkably, 5 oncogenes were overexpressed in the iPSCs and an oncogene RAB25 in the iPSC-differentiated cells, suggesting that these iPSC consensus genes are implicated with the risk of tumorigenesis and cancers. This investigation provides useful information for designing new strategies and methods to curtail the expression of oncogenic genes in iPSCs and produce safe iPSC derivatives for stem cell therapy. © 2012 Mary Ann Liebert, Inc.

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