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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 hyperglycemia on H2O2 production in mice plasma. The levels of H2O2 in mice plasma were tested before the mice were sacrificed. ∗P < 0.05 as compared with euglycemia group; #P < 0.05 as compared with hyperglycemia group.
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fig2: Effect of hyperglycemia on H2O2 production in mice plasma. The levels of H2O2 in mice plasma were tested before the mice were sacrificed. ∗P < 0.05 as compared with euglycemia group; #P < 0.05 as compared with hyperglycemia group.

Mentions: Hyperglycemic condition has been shown to induce the overproduction of reactive oxygen species (ROS), which consists of a number of chemically reactive molecules derived from oxygen, including H2O2 [25]. Our previous in vitro study also proved that H2O2 is able to mediate high glucose-induced invasive activity via ERK and p38 MAPK in human PC cells [13]. In this study, we tested the level of H2O2 in mice plasma before the mice were sacrificed. As shown in Figure 2, hyperglycemic mice contained a higher plasma H2O2 level than that from euglycemic mice. PEG-CAT could significantly reduce the blood H2O2 level of STZ-injected mice.


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 hyperglycemia on H2O2 production in mice plasma. The levels of H2O2 in mice plasma were tested before the mice were sacrificed. ∗P < 0.05 as compared with euglycemia group; #P < 0.05 as compared with hyperglycemia group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Effect of hyperglycemia on H2O2 production in mice plasma. The levels of H2O2 in mice plasma were tested before the mice were sacrificed. ∗P < 0.05 as compared with euglycemia group; #P < 0.05 as compared with hyperglycemia group.
Mentions: Hyperglycemic condition has been shown to induce the overproduction of reactive oxygen species (ROS), which consists of a number of chemically reactive molecules derived from oxygen, including H2O2 [25]. Our previous in vitro study also proved that H2O2 is able to mediate high glucose-induced invasive activity via ERK and p38 MAPK in human PC cells [13]. In this study, we tested the level of H2O2 in mice plasma before the mice were sacrificed. As shown in Figure 2, hyperglycemic mice contained a higher plasma H2O2 level than that from euglycemic mice. PEG-CAT could significantly reduce the blood H2O2 level of STZ-injected mice.

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