Acta Pharmacologica Sinica (2009) 30: 1436–1442; doi: 10.1038/aps.2009.137

Acta Pharmacologica Sinica (2009) 30: 1436–1442; doi: 10.1038/aps.2009.137; published online 14 Sep 2009

Original Article

Upregulation of human DNA binding protein A (dbpA) in gastric cancer cells

Guo-rong WANG^1,2, Yan ZHENG³, Xiang-ming CHE^1,*, Xin-yang WANG⁴, Jia-hui ZHAO⁴, Kai-jie WU⁴, Jin ZENG⁴, Chen-en PAN¹, 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

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), β-catenin and cyclin D1, but had no effect on expression of NF-kB. 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, β-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

We thank Dr KAJINO for kindly providing the anti-dbpA antibody and Dr Mike Chen for his critical review of the manuscript. This research was supported by grants from the National Natural Science Foundation of China (No 30371591) and the Science and Technology Project of Shaan xi Province, China [2005K09-G3(3)].

* To whom correspondence should be addressed.
Email xiangmingche2009@yahoo.cn
Received 2009-06-02 Accepted 2009-08-07

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