Overexpression of ECRG4 enhances chemosensitivity to 5-fluorouracil in the human gastric cancer SGC-7901 cell line
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RESEARCH ARTICLE
Overexpression of ECRG4 enhances chemosensitivity to 5-fluorouracil in the human gastric cancer SGC-7901 cell line Cheng-Ping Jiang & Bi-Hua Wu & Bai-Qiang Wang & Mao-Yong Fu & Ming Yang & Yue Zhou & Fu Liu
Received: 13 March 2013 / Accepted: 22 March 2013 / Published online: 4 April 2013 # International Society of Oncology and BioMarkers (ISOBM) 2013
Abstract The aim of this study was to examine the effects of esophageal cancer-related gene 4 (ECRG4) expression levels on chemotherapeutic sensitivity of gastric cancer cells. A SGC-7901 cell system with tetracycline-inducible ECRG4 expression (SGC-7901/ECRG4) was successfully established. ECRG4 mRNA and protein expression levels were detected using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Chemosensitivity to 5-fluorouracil (5-FU) was examined by cell proliferation assay and cell apoptosis assay. ECRG4 mRNA and protein expression levels were significantly upregulated in SGC-7901/ECRG4 cells induced with tetracycline. Compared with control cells, the growth inhibition rate of cells with ECRG4 overexpression was significantly increased when treated with 5-FU. Treatment with 5 μmol/l 5-FU resulted in 15.2 % apoptotic cells, whereas such treatment after overexpression of ECRG4 resulted in 44.5 % apoptotic cells. In conclusion, overexpression of ECRG4 enhanced the chemosensitivity of gastric cancer SGC-7901 cells to 5-FU through induction of apoptosis. Keywords ECRG4 . Chemosensitivity . 5-FU
Introduction Despite its declining incidence, gastric cancer remains the second most common cause of cancer-related mortality in Asia and worldwide [1, 2]. Surgery remains the mainstay of C.-P. Jiang : B.-H. Wu (*) : B.-Q. Wang : M.-Y. Fu : M. Yang : Y. Zhou : F. Liu Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, No. 63, Wenhua Rd., Nanchong 637000, China e-mail: [email protected]
any curative treatment. However, even following radical surgery, the majority of gastric cancer patients develop local or distant recurrence [3]. Several meta-analyses of postoperative adjuvant trials have demonstrated a significant benefit for chemotherapy-treated patients [4]. However, certain patients have undergone expensive and potentially harmful therapy without gaining any benefit. Thus, the identification of molecular markers in resected tumor tissues that are able to predict outcomes is essential for the future development of adjuvant chemotherapy for gastric cancer patients. Esophageal cancer-related gene 4 (ECRG4), officially called C2ORF40, was cloned and identified from normal esophageal epithelium [5]. It is localized in 2q12.2. The encoded protein (augurin) is a secretory molecule produced in endocrine tissues such as pituitary gland, adrenal gland, and choroid plexus [6]. Its actions consist in cerebrospinal fluid homeostasis, stimulation of neuroprogenitor cells after brain injury [7], and induction of cell senescence in central nervous system [8]. Even if its impact on oncogenesis i
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