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Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide.

Li W, Zhang L, Chen X, Jiang Z, Zong L, Ma Q - Oxid Med Cell Longev (2016)

Bottom Line: In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased.The injection of PEG-CAT could also reverse hyperglycemia-induced EMT.These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

ABSTRACT
Diabetes mellitus (DM) and pancreatic cancer are intimately related, as approximately 85% of patients diagnosed with pancreatic cancer have impaired glucose tolerance or even DM. Our previous studies have indicated that high glucose could promote the invasive and migratory abilities of pancreatic cancer cells. We therefore explored the underlying mechanism that hyperglycemia modulates the metastatic potential of pancreatic cancer. Our data showed that streptozotocin- (STZ-) treated diabetic nude mice exhibit larger tumor size than that of the euglycemic mice. The number of nude mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. Hyperglycemic mice contain a higher plasma H2O2-level than that from euglycemic mice. The injection of polyethylene glycol-conjugated catalase (PEG-CAT), an H2O2 scavenger, may reverse hyperglycemia-induced tumor metastasis. In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased. The injection of PEG-CAT could also reverse hyperglycemia-induced EMT. These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.

No MeSH data available.


Related in: MedlinePlus

Effect of STZ on blood glucose and weight in nude mice. (a) Blood glucose in STZ-treated mice (n = 12). (b) Body weight in STZ-treated mice (n = 12). ∗ refers to P < 0.05 as compared with control group.
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fig1: Effect of STZ on blood glucose and weight in nude mice. (a) Blood glucose in STZ-treated mice (n = 12). (b) Body weight in STZ-treated mice (n = 12). ∗ refers to P < 0.05 as compared with control group.

Mentions: To determine the efficacy of different drugs against transplantation-established human tumor xenografts in the athymic nude mice, we used an orthotopic tumor model. STZ is a chemical which is commonly used to induce experimental diabetes in animals [24]. The characteristics of the STZ-treated nude mice used in this study were summarized in Figure 1. The fasting blood glucose levels were significantly increased from 2 weeks to 4 weeks and keep a high level till 10 weeks after STZ injection (Figure 1(a)). The body weight of the nude mice were reduced at 4 weeks after STZ injection (Figure 1(b)).


Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide.

Li W, Zhang L, Chen X, Jiang Z, Zong L, Ma Q - Oxid Med Cell Longev (2016)

Effect of STZ on blood glucose and weight in nude mice. (a) Blood glucose in STZ-treated mice (n = 12). (b) Body weight in STZ-treated mice (n = 12). ∗ refers to P < 0.05 as compared with control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940572&req=5

fig1: Effect of STZ on blood glucose and weight in nude mice. (a) Blood glucose in STZ-treated mice (n = 12). (b) Body weight in STZ-treated mice (n = 12). ∗ refers to P < 0.05 as compared with control group.
Mentions: To determine the efficacy of different drugs against transplantation-established human tumor xenografts in the athymic nude mice, we used an orthotopic tumor model. STZ is a chemical which is commonly used to induce experimental diabetes in animals [24]. The characteristics of the STZ-treated nude mice used in this study were summarized in Figure 1. The fasting blood glucose levels were significantly increased from 2 weeks to 4 weeks and keep a high level till 10 weeks after STZ injection (Figure 1(a)). The body weight of the nude mice were reduced at 4 weeks after STZ injection (Figure 1(b)).

Bottom Line: In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased.The injection of PEG-CAT could also reverse hyperglycemia-induced EMT.These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

ABSTRACT
Diabetes mellitus (DM) and pancreatic cancer are intimately related, as approximately 85% of patients diagnosed with pancreatic cancer have impaired glucose tolerance or even DM. Our previous studies have indicated that high glucose could promote the invasive and migratory abilities of pancreatic cancer cells. We therefore explored the underlying mechanism that hyperglycemia modulates the metastatic potential of pancreatic cancer. Our data showed that streptozotocin- (STZ-) treated diabetic nude mice exhibit larger tumor size than that of the euglycemic mice. The number of nude mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. Hyperglycemic mice contain a higher plasma H2O2-level than that from euglycemic mice. The injection of polyethylene glycol-conjugated catalase (PEG-CAT), an H2O2 scavenger, may reverse hyperglycemia-induced tumor metastasis. In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased. The injection of PEG-CAT could also reverse hyperglycemia-induced EMT. These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.

No MeSH data available.


Related in: MedlinePlus