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Background: Recently Cyclophilin A (CypA) was identified as a candidate target protein in gastric carcinoma. However, the role of CypA in gastric cancer (GC) has not been investigated extensively so far. Aim: The purpose of this study was to determine the expression pattern of CypA in human GC, and to explore the effects of suppressed CypA expression on cell proliferation and xenografted tumor growth of gastric cancer. Methods: In the present study, we detected the expression pattern of CypA in human GC by immunohistochemistry analysis. Further, the RNAi method was used to silence CypA, and colony formation assay, growth curves, cell cycle and mouse xenograft were analysed. Results: An elevated expression of CypA in GC tissues compared with normal gastric mucosa was observed, especially in TNM stage-I and intestinal type of tumor. CypA was overexpressed in most GC cell lines and endogenous expression of CypA correlated with cell growth phenotypes. Transient suppression of CypA reduced the proliferation of BGC-823 and SGC-7901 GC cell lines. Exogenous CypA promoted the proliferation of NCI-N87 GC cells in a concentration dependent manner. Further study revealed that stable CypA silencing inhibited the proliferation, prevented cell cycle and reduced autophagy of BGC-823 GC cells in vitro through suppressing the ERK1/2 signal pathway. Stable CypA silencing also inhibited the growth of xenografted tumor of BGC-823 GC cell in nude mice. Conclusions: These results indicate a special function mode for CypA of playing more important roles in the early stage of gastric tumorigenesis and suggest CypA as a new molecular target of diagnosis and treatment for GC patients. [ABSTRACT FROM AUTHOR]

AbstractLow-dose metronomic (LDM) chemotherapy represents a new strategy to treat solid tumors by stronger antiangiogenic activity and less side-effects, especially in combination with other antiangiogenic agents. The aim of the study is to investigate the antiangiogenic effect of docetaxel alone and combined with (−)-epigallocatechin-3-gallate (EGCG) in preclinical settings of gastric cancer. BGC-823 human gastric cancer xenograft model was used, and tumor growth, side-effects of mice were closely monitored. Expression of vascular endothelial growth factor and CD31 were observed by immunohistochemistry, and microvessel density of the tumor tissues was assessed by CD31 immunohistochemical analysis. Our results indicated that LDM docetaxel inhibited angiogenesis and growth of gastric cancer with less toxicity, and the effects were further enhanced by the concurrent administration of EGCG. Our study, for the first time, rationally demonstrated that LDM docetaxel treatment used alone or combined with EGCG is effective and safe in preclinical settings of gastric cancer. Our data suggest that LDM docetaxel used alone or combined with EGCG may be an innovative and promising therapeutic strategy in the experimental treatment of human gastric cancer. [ABSTRACT FROM AUTHOR]