title: The impact of insulin on chemotherapeutic sensitivity to 5-fluorouracil in gastric cancer cell lines SGC7901, MKN45 and MKN28.
abstract: BACKGROUND
  The role of insulin in the pathogenesis of cancer has been increasingly emphasized because of the high incidence of obesity and metabolic syndrome and their correlated complication including cancer. This study aimed to explore the impact of insulin on chemoresistance to 5-fluorouracil in gastric cancer and the possible mechanisms.
  
  
  METHODS
  Tissue samples of gastric cancer and adjacent normal gastric mucosa from patients with or without obesity were performed immunohistochemical staining for P-glycoprotein. The follow-up was done after the surgical treatment. The effect of insulin on chemotherapeutic sensitivity of the three gastric cancer cell lines to 5-fluorouracil was evaluated by pre-incubation with insulin before administration of 5-fluorouracil. The expression of P-glycoprotein was determined by Western blotting.
  
  
  RESULTS
  P-glycoprotein were overexpressed in tissues from patients who suffered gastric cancer and were higher in those simultaneously suffered gastric cancer and obesity. Addition of 1 μM insulin remarkably promoted the proliferation of SGC7901, MKN45 and MKN28 cells and decreased the cytotoxicity of 5-fluorouracil. In addition, the expression of P-glycoprotein was upregulated in SGC7901, MKN45 and MKN28 cells.
  
  
  CONCLUSIONS
  Insulin improved the proliferation of gastric cancer cell lines and contributed to chemoresistance of gastric cancer cells to 5-fluorouracil which is likely to involve upregulation of P-glycoprotein.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. zhaowei9803@126.com.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. zhaowei9803@126.com.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. len311212@163.com.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. len311212@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. doctorljs@sina.com.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. doctorljs@sina.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Junsong
authors.affiliation: Department of Neonatal Surgery, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, P.R.China. 121169041@qq.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Rui
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. changshuai.2009@stu.xjtu.edu.cn.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. changshuai.2009@stu.xjtu.edu.cn.
authors.forename: Chang
authors.initials: C
authors.lastname: Shuai
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. qgl861215@163.com.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. qgl861215@163.com.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Guanglin
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. hsc099@stu.xjtu.edu.cn.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. hsc099@stu.xjtu.edu.cn.
authors.forename: He
authors.initials: H
authors.lastname: Shicai
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. 377199266@qq.com.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. 377199266@qq.com.
authors.forename: Wang
authors.initials: W
authors.lastname: Zexing
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. 804834843@qq.com.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. 804834843@qq.com.
authors.forename: Wang
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. chexiang@mail.xjtu.edu.cn.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. chexiang@mail.xjtu.edu.cn.
authors.forename: Che
authors.initials: C
authors.lastname: Xiangming
authors.affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. dawn@mail.xjtu.edu.cn.|Health science center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. dawn@mail.xjtu.edu.cn.
authors.forename: Wang
authors.initials: W
authors.lastname: Shufeng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D008297:Male; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007328:Insulin; D005472:Fluorouracil