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The impact of insulin on chemotherapeutic sensitivity to 5-fluorouracil in gastric cancer cell lines SGC7901, MKN45 and MKN28.

Wei Z, Liang L, Junsong L, Rui C, Shuai C, Guanglin Q, Shicai H, Zexing W, Jin W, Xiangming C, Shufeng W - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: The expression of P-glycoprotein was determined by Western blotting.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.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. zhaowei9803@126.com.

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.

No MeSH data available.


Related in: MedlinePlus

Cell viability of gastric cancer cell lines with administration of different concentrations of 5-fluorouracil and insulin. Graph A show the proliferation rate of SGC7901, MKN45, MKN28 cells in contrast to GES cells in 48 hours after administration of different concentrations of 5-Fu with high, normal or without insulin. B and C shows the photographs of three gastric cancer cell lines and the control GES cells in the conditions of 5-fluorouracil and different concentrations of insulin at 72 hours.
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Fig4: Cell viability of gastric cancer cell lines with administration of different concentrations of 5-fluorouracil and insulin. Graph A show the proliferation rate of SGC7901, MKN45, MKN28 cells in contrast to GES cells in 48 hours after administration of different concentrations of 5-Fu with high, normal or without insulin. B and C shows the photographs of three gastric cancer cell lines and the control GES cells in the conditions of 5-fluorouracil and different concentrations of insulin at 72 hours.

Mentions: Since results above showed that high level of insulin promoted gastric cancer cells growth and 5-fluorouracil was therapeutically effective to gastric cancer cells, we then examined whether high insulin induced chemoresistance to 5-fluorouracil in gastric cancer cells. The number of live cells was measured by CCK-8 assay as described above. In the presence of 1 μM of insulin, the toxic effect of 5-fluorouracil on gastric cancer cells was apparently compromised and cell number was much more after treatment than with low concentration of insulin or without insulin. This phenomenon did not disappear until the concentration of 5-fluorouracil was added up to 100 μg/ml (Figure 4).Figure 4


The impact of insulin on chemotherapeutic sensitivity to 5-fluorouracil in gastric cancer cell lines SGC7901, MKN45 and MKN28.

Wei Z, Liang L, Junsong L, Rui C, Shuai C, Guanglin Q, Shicai H, Zexing W, Jin W, Xiangming C, Shufeng W - J. Exp. Clin. Cancer Res. (2015)

Cell viability of gastric cancer cell lines with administration of different concentrations of 5-fluorouracil and insulin. Graph A show the proliferation rate of SGC7901, MKN45, MKN28 cells in contrast to GES cells in 48 hours after administration of different concentrations of 5-Fu with high, normal or without insulin. B and C shows the photographs of three gastric cancer cell lines and the control GES cells in the conditions of 5-fluorouracil and different concentrations of insulin at 72 hours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4494778&req=5

Fig4: Cell viability of gastric cancer cell lines with administration of different concentrations of 5-fluorouracil and insulin. Graph A show the proliferation rate of SGC7901, MKN45, MKN28 cells in contrast to GES cells in 48 hours after administration of different concentrations of 5-Fu with high, normal or without insulin. B and C shows the photographs of three gastric cancer cell lines and the control GES cells in the conditions of 5-fluorouracil and different concentrations of insulin at 72 hours.
Mentions: Since results above showed that high level of insulin promoted gastric cancer cells growth and 5-fluorouracil was therapeutically effective to gastric cancer cells, we then examined whether high insulin induced chemoresistance to 5-fluorouracil in gastric cancer cells. The number of live cells was measured by CCK-8 assay as described above. In the presence of 1 μM of insulin, the toxic effect of 5-fluorouracil on gastric cancer cells was apparently compromised and cell number was much more after treatment than with low concentration of insulin or without insulin. This phenomenon did not disappear until the concentration of 5-fluorouracil was added up to 100 μg/ml (Figure 4).Figure 4

Bottom Line: The expression of P-glycoprotein was determined by Western blotting.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.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R.China. zhaowei9803@126.com.

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.

No MeSH data available.


Related in: MedlinePlus