Key Laboratory for Gastrointestinal Disease of Gansu Province

Fort-de-France, Martinique

Key Laboratory for Gastrointestinal Disease of Gansu Province

Fort-de-France, Martinique
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Liu X.-J.,Lanzhou University | Liu X.-J.,Key Laboratory for Gastrointestinal Disease of Gansu Province | Chen Z.-F.,Lanzhou University | Chen Z.-F.,Key Laboratory for Gastrointestinal Disease of Gansu Province | And 11 more authors.
World Journal of Gastroenterology | Year: 2013

Aim: To investigate the mechanisms of how cyclooxygenase- 2 (COX-2) regulates E-cadherin in gastric cancer cells. Methods: COX-2 expression in human gastric cancer cell lines SGC-7901, BGC-823, MGC-803 and AGS were measured at the mRNA and protein level. COX-2 rich cell line SGC-7901 was chosen for subsequent experiments. siRNA mediated gene knockdown was used to investigate the impact of COX-2 on nuclear factor-κB (NF-κB), Snail, and E-cadherin in gastric cancer cells. Gene expression was determined by Western blot and real-time polymerase chain reaction. To analyze whether NF-κB inhibition could interrupt the modulatory effect of COX-2 or prostaglandin E2 (PGE2) on E-cadherin, gastric cancer cells were treated with celecoxib or PGE2, in the presence of NF-κB specific siRNA. Results: Highest expression level of COX-2 was found in SGC-7901 cells, both at mRNA and protein levels. siRNA mediated down-regulation of COX-2 led to a reduced expression of NF-κB and Snail, but an increased expression of E-cadherin in SGC-7901 cells. siRNA mediated down-regulation of NF-κB also led to a reduced expression of E-cadherin and Snail in SGC-7901 cells. However, COX-2 expression did not alter after cells were treated with NF-κB specific siRNA in SGC-7901 cells. Treatment of SGC-7901 cells with celecoxib led to a reduced expression of Snail but an increased expression of E-cadherin. In contrast, treatment of SGC-7901 cells with PGE2 led to an increased Snail and a decreased E-cadherin. However, siRNAmediated knockdown of NF-κB partially abolished the effect of celecoxib and PGE2 on the regulation of E-cadherin and Snail in SGC-7901 cells. Conclusion: COX-2 likely functions upstream of NF- κB and regulates the expression of E-cadherin via NF- κB/Snail signaling pathway in gastric cancer cells. © 2013 Baishideng. All rights reserved.


Liu X.,Lanzhou University | Liu X.,Key Laboratory for Gastrointestinal Disease of Gansu Province | Yang Z.,Lanzhou University | Chen Z.,Key Laboratory for Gastrointestinal Disease of Gansu Province | And 7 more authors.
Oncology Reports | Year: 2015

Lactate dehydrogenase A (LDH-A), which regulates glycolytic flux by catalyzing pyruvate to lactate in the cytoplasm, is believed to be one of the highly attractive therapeutic targets for cancers. Firstly, we detected the expression of LDH-A in gastric cancer (GC) cells. LDH-A inhibitor oxamate was then used to suppress the LDH-A activity in GC cells. Cell proliferation, lactic acid production, Transwell migration assay and apoptosis were assessed, respectively. The results showed that inhibition of LDH-A by oxamate decreased the lactate production. In the presence of glucose, oxamate inhibited cell proliferation in a dose-dependent manner. Flow cytometry assay further confirmed a pro-apoptotic effect of oxamate, and this was likely through increased expression of Bax, activated caspase-3, and decreased expression of Bcl-2. Therefore, we believe that oxamate inhibits cell growth, suppresses tumor invasion, and induces apoptosis in GC cells. LDH-A may be a potential therapeutic target for GC.


PubMed | Key Laboratory for Gastrointestinal Disease of Gansu Province, University of Sydney and Lanzhou University
Type: Journal Article | Journal: Oncology reports | Year: 2014

Lactate dehydrogenase A (LDH-A), which regulates glycolytic flux by catalyzing pyruvate to lactate in the cytoplasm, is believed to be one of the highly attractive therapeutic targets for cancers. Firstly, we detected the expression of LDH-A in gastric cancer (GC) cells. LDH-A inhibitor oxamate was then used to suppress the LDH-A activity in GC cells. Cell proliferation, lactic acid production, Transwell migration assay and apoptosis were assessed, respectively. The results showed that inhibition of LDH-A by oxamate decreased the lactate production. In the presence of glucose, oxamate inhibited cell proliferation in a dose-dependent manner. Flow cytometry assay further confirmed a pro-apoptotic effect of oxamate, and this was likely through increased expression of Bax, activated caspase-3, and decreased expression of Bcl-2. Therefore, we believe that oxamate inhibits cell growth, suppresses tumor invasion, and induces apoptosis in GC cells. LDH-A may be a potential therapeutic target for GC.


Guo Q.,Key Laboratory for Gastrointestinal Disease of Gansu Province | Lu H.,Key Laboratory for Gastrointestinal Disease of Gansu Province | Wang J.,Key Laboratory for Gastrointestinal Disease of Gansu Province | Chen Z.,Key Laboratory for Gastrointestinal Disease of Gansu Province | And 6 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2016

This study aims to investigate the association between transporter associated with antigen processing 1 gene (TAP1) polymorphism and esophagus cancer in a Han Gansu population. TAP1 637A/G polymorphism was analyzed in 200 Han Gansu patients with esophagus cancer and 100 ethnically matched healthy Gansu population by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The adjusted odds ratios (OR) and 95% confidence intervals (CI) were performed by logistic regression model. The results indicated that significant difference was observed in genetype frequencies of TAP1 polymorphisms (AA, AG and GG) between esophagus cancer patients and normal subjects (P=0.045). However, only AG genotype was significantly elevated in esophagus cancer compared with controls (35 vs. 23%; P=0.035; OR=2.8), suggesting a significant positive association with esophagus cancer susceptibility. Meanwhile, AG genotype was found to be associated with gender, age, lymph node metastasis and distant metastasis (P<0.05) but rather than with smoke history and tumor size in esophagus cancer. In conclusion, TAP1 637-Asp/Gly polymorphism correlates with the risk of esophagus cancer in a Han Gansu population, which might be served as a genetic susceptibility marker in esophagus cancer patients. © 2016, E-Century Publishing Corporation. All rights reserved.

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