Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide.
Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide.
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高血糖通过过氧化氢促进胰腺癌的上皮-间质转化
DOI：
10.1155/2016/5190314
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发表时间：
2016
影响因子：
--
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Li W;Zhang L;Chen X;Jiang Z;Zong L;Ma Q
糖尿病（DM）和胰腺癌密切相关，因为大约85%的胰腺癌患者患有葡萄糖耐量受损甚至DM。我们前期的研究表明，高糖可促进胰腺癌细胞的侵袭和迁移能力。因此，我们探讨了高血糖调节胰腺癌转移潜力的潜在机制。我们的数据表明，链脲佐菌素（STZ）治疗的糖尿病裸鼠表现出更大的肿瘤大小比血糖正常的小鼠。STZ治疗组裸鼠肝转移或腹水发生率明显高于血糖正常组。高血糖小鼠的血浆H2 O2水平高于正常血糖小鼠。注射H2 O2清除剂聚乙二醇结合过氧化氢酶（PEG-CAT）可逆转高血糖诱导的肿瘤转移。此外，高血糖还可调节胰腺癌组织中上皮-间质转化相关因子的表达，如E-cadherin水平降低，间质标志物N-cadherin和vimentin以及转录因子snail的表达显著增加。注射PEG-CAT也可逆转高血糖诱导的EMT。这些结果表明，高血糖症和胰腺癌预后不良之间的关联可以归因于EMT通过过氧化氢的产生的改变。
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.