Hai-Chen Xu

Nanjing Medical University, Nan-ching, Jiangsu Sheng, China

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Publications (6)15.24 Total impact

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    ABSTRACT: Gastrin, cholecystokinin2 receptor (CCK2R), and cyclooxygenase-2 (COX-2) have been implicated in the carcinogenesis and progression of gastric cancer. Our study demonstrated that antagonist or siRNA against CCK2R blocked amidated gastrin (G17)-induced activation of STAT3 and Akt in gastric cancer cell lines. G17-increased COX-2 expression and cell proliferation were effectively blocked by CCK2R antagonist and inhibitors of JAK2 and PI3K. In addition, knockdown of STAT3 expression significantly attenuated G17-induced PI3K/Akt activation, COX-2 expression, and cell proliferation. These results suggest that CCK2R-mediated COX-2 up-regulation via JAK2/STAT3/PI3K/Akt pathway is involved in the proliferative effect of G17 on human gastric cancer cells.
    Cancer letters 01/2013; 332(1). DOI:10.1016/j.canlet.2012.12.030 · 5.62 Impact Factor
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    ABSTRACT: Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. It has been demonstrated that COX-2 overexpression depends on different cellular pathways, involving both transcriptional and post-transcriptional regulation. MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators. Here, we characterize miR-101 expression and its role in the regulation of COX-2 expression, which in turn, will provide us with additional insights into the potential therapeutic benefits of exogenous miR-101 for treatment of gastric cancer. Our results showed that miR-101 levels in gastric cancer tissues were significantly lower than those in the matched normal tissue (P < 0.01). Furthermore, lower levels of miR-101 were associated with increased tumor invasion and lymph node metastasis (P < 0.05). We also found an inverse correlation between miR-101 and COX-2 expression in both gastric cancer specimens and cell lines. Significant decreases in COX-2 mRNA and COX-2 levels were observed in the pre-miR-101-infected gastric cancer cells. One possible mechanism of interaction is that miR-101 inhibited COX-2 expression by directly binding to the 3'-UTR of COX-2 mRNA. Overexpression of miR-101 in gastric cancer cell lines also inhibited cell proliferation and induced apoptosis in vitro, as well as inhibiting tumor growth in vivo. These results collectively indicate that miR-101 may function as a tumor suppressor in gastric cancer, with COX-2 as a direct target.
    FEBS Journal 09/2012; 279(22). DOI:10.1111/febs.12013 · 4.00 Impact Factor
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    ABSTRACT: Although inhibition of cyclooxygenase-2 (COX-2) or activation of peroxisome proliferators-activated receptor gamma (PPAR-gamma) leads to growth inhibition in malignancies, the synergistic anti-tumor effects of combination of COX-2 inhibitor (NS-398) and PPAR-gamma agonist (rosiglitazone) on the human pancreatic cancer cells remains unknown. Here, we evaluated the effects of NS-398 and/or rosiglitazone on the cell proliferation and apoptosis in a pancreatic cancer cell line, SW1990. NS-398 and rosiglitazone decreased cell proliferation in a dose- and time-dependent manner. Proliferating cell nuclear antigen (PCNA) labeling index significantly decreased in the cells treated with either NS-398 or rosiglitazone. Both NS-398 and rosiglitazone alone induced apoptotic cell death of SW1990. The combination of NS-398 and rosiglitazone exerted synergistic effects on proliferation inhibition, and apoptosis induction in SW1990 cells, with down-regulation of Bcl-2 and up-regulation of Bax expression. Our results indicate that simultaneous targeting of COX-2 and PPAR-gamma inhibits pancreatic cancer development more effectively than targeting each molecule alone.
    Cancer letters 03/2009; 275(2):247-55. DOI:10.1016/j.canlet.2008.10.023 · 5.62 Impact Factor
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    ABSTRACT: To investigate the regulative roles of the gastrin receptor antagonist proglumide and the specific cyclooxygenase (COX)-2 inhibitor NS-398 on the proliferation and apoptosis of gastric cancer cells. Human gastric cancer cells of the line MKN-45 were routinely cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. Subconfluent cell cultures were treated with proglumide at a final concentration of 5 mmol/L, NS-398 at a final concentration of 10.0 micromol/L, or proglumide in combination with NS-398 for 48 h. The growth and proliferation of MKN-45 cells were analyzed with MTT assay. Flow cytometric analysis was used to detect the apoptosis of the gastric cancer cells. RT-PCR and Western blotting were used to detect the expression of apoptosis-inhibited gene bcl-2 mRNA and protein. The apoptosis rates of the cells treated by proglumide, NS-398, and combination of two agents were 24.7% +/- 3.2%, 26.7% +/- 3.4%, and 36.1% +/- 4.6% respectively, all significantly higher than that in the control group (1.6% +/- 0.6%, all P < 0.01). The apoptosis rates of the MKN-45 cells treated with proglumide combined with NS-398 was significantly greater than those of the cells treated by the two agents alone (both P < 0.05). Treatment with proglumide and NS-398 significantly reduced the bcl-2 mRNA and protein expression in the MKN-45 cells (P < 0.05). Both proglumide and NS-398 inhibit the proliferation and induce the apoptosis of human gastric cells. This apoptosis may be mediated by down-regulation of the expression of apoptosis-inhibited gene bcl-2. Co-treatment with proglumide and NS-398 have synergistic anticancer role.
    Zhonghua yi xue za zhi 01/2006; 86(4):250-4.
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    ABSTRACT: AIM: To investigate the expression of cyclooxygenase-2 (COX-2) and its correlation with the angiogenesis and clinicopathological features in esophageal carcinoma. METHODS: Ninety tumor specimens resected from patients with squamous cell carcinoma of the esophagus were obtained, and 34 corresponding paracancerous normal tissues were randomly selected as the controls. Immunohistochemical staining was used to detect the expression of COX-2. Monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was determined by counting the CD34-positive cells. The correlations of COX-2 expression with MVD and clinicopathological parameters of the patients were analyzed. RESULTS: The positive rates of COX-2 and MVD expression in the cancerous tissue were 84.4% and 29.68 ± 3.81, respectively, which were significantly higher than those in the normal esophageal mucosa (20.6%, χ2 = 45.47, P = 0.00; 15.12 ± 2.80, t = 20.28, P = 0.00). COX-2 expression was closely correlated with clinical TNM classification (χ2 = 7.99, P = 0.005), cellular differentiation (χ2 = 7.99, P = 0.005) and lymph node metastasis (χ2 = 9.61, P = 0.002) in squamous cell carcinoma of the esophagus. The mean values of MVD were associated with clinical TNM classification (t = -7.09, P = 0.00) and lymph node metastasis (t = -7.90, P = 0.00). The spearman rank correlation test showed that tumor MVD was positively associated with COX-2 expression (r = 0.607, P = 0.00). CONCLUSION: Over-expression of COX-2 is correlated with tumor invasion and lymph node metastasis in esophageal carcinoma, suggesting that COX-2 contributes to the development of esophageal cancer by promoting angiogenesis.
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    ABSTRACT: To investigate COX-2 expression in patients with gastric cancer and its relationship with angiogenesis and clinicopathologic features of gastric cancer. COX-2 expression and CD34-stained microvessel density (MVD) were detected by immunohistochemical methods in specimens from 96 patients with gastric cancer. The correlations among COX-2 expression, MVD and clinicopathologic features were analyzed. The COX-2 positive rate and MVD in gastric cancer were significantly higher than those in the normal gastric mucosa (80.2% vs. 13.3%; 32.5+/- 8.3 vs. 13.1+/- 2.4, all P< 0.01). The COX-2 positive rate and MVD in the patients with stage III and IV were significantly higher (91.4% and 34.9+/- 8.7 respectively, P< 0.01), than that in the patients with stage I and II. The COX-2 positive rate and MVD in the cases with lymph node metastasis were 87.9% and (35.0+/- 8.5) respectively, higher than those in the cases without lymph node metastasis (P< 0.05). The Spearman rank correlation test showed a significant correlation between COX-2 expression and tumor MVD (r=0.311, P< 0.01). COX-2 plays an important role in gastric cancer angiogenesis. COX-2 and angiogenesis induced by COX-2 contribute to tumor invasion and lymph node metastasis.
    Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 07/2005; 8(4):343-7.

Publication Stats

76 Citations
15.24 Total Impact Points


  • 2009-2013
    • Nanjing Medical University
      • • Department of Gastroenterology
      • • Department of Geriatrics
      Nan-ching, Jiangsu Sheng, China