title: Knockdown of asparagine synthetase (ASNS) suppresses cell proliferation and inhibits tumor growth in gastric cancer cells.
abstract: OBJECTIVE
  Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine. ASNS is deemed as a promising therapeutic target and its expression is associated with the chemotherapy resistance in several human cancers. However, its role in gastric cancer tumorigenesis has not been investigated.
  
  
  METHODS
  In this study, we employed small interfering RNA (siRNA) to transiently knockdown ASNS in two gastric cancer cell lines, AGS and MKN-45, followed by growth rate assay and colony formation assay. Dose response curve analysis was performed in AGS and MKN-45 cells with stable ASNS knockdown to assess sensitivity to cisplatin. Xenograft experiment was performed to examine in vivo synergistic effects of ASNS depletion and cisplatin on tumor growth. Expression level of ASNS was evaluated in human patient samples using quantitative PCR. Kaplan-Meier curve analysis was performed to evaluate association between ASNS expression and patient survival.
  
  
  RESULTS
  Transient knockdown of ASNS inhibited cell proliferation and colony formation in AGS and MKN-45 cells. Stable knockdown of ASNS conferred sensitivity to cisplatin in these cells. Depletion of ASNS and cisplatin treatment exerted synergistic effects on tumor growth in AGS xenografts. Moreover, ASNS was found to be up-regulated in human gastric cancer tissues compared with matched normal colon tissues. Low expression of ASNS was significantly associated with better survival in gastric cancer patients.
  
  
  CONCLUSIONS
  ASNS may contribute to gastric cancer tumorigenesis and may represent a novel therapeutic target for prevention or intervention of gastric cancer.
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , PR China.
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Yu
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , PR China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zheng
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , PR China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , PR China.
authors.forename: Bangmao
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D001217:Aspartate-Ammonia Ligase / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics*; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D001217:Aspartate-Ammonia Ligase; D002945:Cisplatin
keywords: Asparagine synthetase; chemo-sensitivity; gastric cancer; tumor progression