Wenhua Feng1, Yan Xin, Yuping Xiao, Wenhui Li, Dan Sun. 1. Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China, whfeng@lnszjk.com.cn.
Abstract
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.
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.
Authors: Michael J Campa; Michael Z Wang; Brandon Howard; Michael C Fitzgerald; Edward F Patz Journal: Cancer Res Date: 2003-04-01 Impact factor: 12.701
Authors: Min Li; Qihui Zhai; Uddalak Bharadwaj; Hao Wang; Fei Li; William E Fisher; Changyi Chen; Qizhi Yao Journal: Cancer Date: 2006-05-15 Impact factor: 6.860
Authors: John Colgan; Mohammed Asmal; Martha Neagu; Bin Yu; Jason Schneidkraut; Youngnam Lee; Elena Sokolskaja; Amy Andreotti; Jeremy Luban Journal: Immunity Date: 2004-08 Impact factor: 31.745
Authors: Veronica Seccia; Elena Navari; Elena Donadio; Claudia Boldrini; Federica Ciregia; Maurizio Ronci; Antonio Aceto; Iacopo Dallan; Antonio Lucacchini; Augusto Pietro Casani; Maria Rosa Mazzoni; Laura Giusti Journal: Head Neck Pathol Date: 2019-05-16
Authors: Viralkumar Davra; Sushil Kumar; Tamjeed Saleh; Ke Geng; Stanley Kimani; Dhriti Mehta; Canan Kasikara; Brendan Smith; Nicholas W Colangelo; Bryan Ciccarelli; Hong Li; Edouard I Azzam; Charalampos G Kalodimos; Raymond B Birge Journal: Mol Cancer Res Date: 2020-04-22 Impact factor: 5.852