The impact of insulin on chemotherapeutic sensitivity to 5-fluorouracil in gastric cancer cell lines SGC7901, MKN45 and MKN28 |
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Authors: | Zhao Wei Li Liang Liu Junsong Chen Rui Chang Shuai Qiu Guanglin He Shicai Wang Zexing Wang Jin Che Xiangming Wang Shufeng |
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Institution: | .Department of General Surgery, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi 710061 P.R.China ;.Health science center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061 P.R.China ;.Department of Neonatal Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003 P.R.China |
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Abstract: | BackgroundThe 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.MethodsTissue 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.ResultsP-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.ConclusionInsulin 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. |
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Keywords: | Gastric cancer Chemoresistance 5-fluorouracil Insulin P-glycoprotein |
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