Original Article
Acta Pharmacologica Sinica (2009) 30: 1436–1442; doi: 10.1038/aps.2009.137; published online 14 Sep 2009
Upregulation of human DNA binding protein A (dbpA) in gastric cancer cells
Guo-rong Wang1,2, Yan Zheng3, Xiang-ming Che1, Xin-yang Wang4, Jia-hui Zhao4, Kai-jie Wu4, Jin Zeng4, Chen-en Pan1 and Da-lin He4
- 1Department of General Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China
- 2Department of General Surgery, People's Hospital of Shaanxi Province, Xi'an 710068, China
- 3Department of Dermatology, Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710004, China
- 4Institute of Urology, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China
Correspondence: Xiang-ming Che, E-mail xiangmingche2009@yahoo.cn
Received 2 June 2009; Accepted 7 August 2009; Published online 14 September 2009.
Abstract
Aim:
To determine the effect of human DNA binding protein (dbpA) on the biology of gastric cancer cells.
Methods:
DbpA expression was analyzed by Western blot analysis and immunofluorescence staining in gastric cancer tissues and cell lines. A dbpA-specific small interference (si) RNA was designed and synthesized. Suppressive effect of siRNA on dbpA expression was assessed by real-time RT-PCR. Transwell migration and colony formation assays were used to assess the inhibitory effects of dbpA siRNA on cell invasion and tumorigenesis in vitro. Drug-sensitivity was evaluated using a conventional 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.
Results:
The expression of dbpA was upregulated in gastric cancer tissues and cell lines as compared to adjacent normal tissues or gastric epithelial cells. siRNA treatment successfully silenced dbpA expression. Silencing of dbpA increased expression of E-cadherin, decreased expression of adenomatous polyposis coli (APC), 
-catenin and cyclin D1, but had no effect on expression of NF-
B. Silencing of dbpA also suppressed cell invasion and colony formation of SGC7901 cells, and enhanced their chemosensitivity to 5-fluorouracil.
Conclusion:
DbpA plays an important role in the pathogenesis and development of gastric cancer, and the process involves E-cadherin, APC, -catenin and cyclin D1. Silencing of dbpA might be a novel therapeutic strategy for increasing chemosensitivity to 5-fluorouracil in gastric cancer.
Keywords:
stomach neoplasms, CSDA protein, human, small interfering RNA, fluorouracil
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