1. The impact of insulin on chemotherapeutic sensitivity to 5-fluorouracil in gastric cancer cell lines SGC7901, MKN45 and MKN28
- Author
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Chang Shuai, Che Xiangming, He Shicai, Chen Rui, Wang Jin, Zhao Wei, Wang Zexing, Liu Junsong, Wang Shufeng, Qiu Guang-lin, and Li Liang
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,P-glycoprotein ,Downregulation and upregulation ,Stomach Neoplasms ,Internal medicine ,Cell Line, Tumor ,medicine ,Insulin ,Humans ,5-fluorouracil ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Cell Proliferation ,Cell growth ,business.industry ,Cancer ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,Fluorouracil ,Apoptosis ,Cancer cell ,Female ,Metabolic syndrome ,business ,Gastric cancer ,Chemoresistance ,medicine.drug ,Research Article - 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. Conclusion 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.
- Published
- 2015