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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

Immunohistochemical staining in adjacent normal mucosa and gastric cancer tissues. A and B were adjacent normal mucosa while C,D,E and F were gastric cancer tissues within which E and F were from patient who simultaneously suffered gastric cancer and obesity. The original tissues of C—F were evaluated to be grade I tumor according to the 3rd Japanese classification of gastric carcinoma. C and D were considered to be diffuse type in Lauren Classification of gastric cancer whereas E and F were intestinal type. The follow-up was showed by graph G within which the red foldline stands for gastric cancer & obesity group and the green one represents gastric cancer group.
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Fig1: Immunohistochemical staining in adjacent normal mucosa and gastric cancer tissues. A and B were adjacent normal mucosa while C,D,E and F were gastric cancer tissues within which E and F were from patient who simultaneously suffered gastric cancer and obesity. The original tissues of C—F were evaluated to be grade I tumor according to the 3rd Japanese classification of gastric carcinoma. C and D were considered to be diffuse type in Lauren Classification of gastric cancer whereas E and F were intestinal type. The follow-up was showed by graph G within which the red foldline stands for gastric cancer & obesity group and the green one represents gastric cancer group.

Mentions: P-glycoprotein expression in gastric cancer was determined by immunohistochemical staining. P-glycoprotein expression was observed as brown-yellow particles in the cell membrane and cytoplasm (Figure 1). The rate of positive P-glycoprotein expression in those patients with gastric cancer and obesity was 94.4% (17/18) compared with 60.9% (14/23) in those with only gastric cancer as controls (p < 0.05). The follow-up showed a longer survival time of those nonobese patients with gastric cancer than those suffered simultaneously gastric cancer and obesity (gastric cancer 11 ± 2.108 vs. gastric cancer & obesity 4 ± 0.585, Log Rank = 14.694, p < 0.05).Figure 1


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)

Immunohistochemical staining in adjacent normal mucosa and gastric cancer tissues. A and B were adjacent normal mucosa while C,D,E and F were gastric cancer tissues within which E and F were from patient who simultaneously suffered gastric cancer and obesity. The original tissues of C—F were evaluated to be grade I tumor according to the 3rd Japanese classification of gastric carcinoma. C and D were considered to be diffuse type in Lauren Classification of gastric cancer whereas E and F were intestinal type. The follow-up was showed by graph G within which the red foldline stands for gastric cancer & obesity group and the green one represents gastric cancer group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Immunohistochemical staining in adjacent normal mucosa and gastric cancer tissues. A and B were adjacent normal mucosa while C,D,E and F were gastric cancer tissues within which E and F were from patient who simultaneously suffered gastric cancer and obesity. The original tissues of C—F were evaluated to be grade I tumor according to the 3rd Japanese classification of gastric carcinoma. C and D were considered to be diffuse type in Lauren Classification of gastric cancer whereas E and F were intestinal type. The follow-up was showed by graph G within which the red foldline stands for gastric cancer & obesity group and the green one represents gastric cancer group.
Mentions: P-glycoprotein expression in gastric cancer was determined by immunohistochemical staining. P-glycoprotein expression was observed as brown-yellow particles in the cell membrane and cytoplasm (Figure 1). The rate of positive P-glycoprotein expression in those patients with gastric cancer and obesity was 94.4% (17/18) compared with 60.9% (14/23) in those with only gastric cancer as controls (p < 0.05). The follow-up showed a longer survival time of those nonobese patients with gastric cancer than those suffered simultaneously gastric cancer and obesity (gastric cancer 11 ± 2.108 vs. gastric cancer & obesity 4 ± 0.585, Log Rank = 14.694, p < 0.05).Figure 1

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