High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer
High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer
复制标题
高葡萄糖微环境通过 SREBP1-自噬轴加速胰腺癌肿瘤生长
DOI：
10.1186/s13046-019-1288-7
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发表时间：
2019-07-11
影响因子：
11.3
通讯作者：
Li, Xuqi
中科院分区：
文献类型：
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作者：
Zhou, Cancan;Qian, Weikun;Li, Xuqi
背景糖尿病是胰腺癌的危险因素，但其发病机制尚未完全阐明。固醇调节元件结合蛋白1（SREBP 1）是一种重要的转录因子，参与脂质代谢和肿瘤进展。然而，高糖微环境，SREBP 1和胰腺癌之间的关系仍有待探讨。胰腺癌细胞系BxPc-3和MiaPaCa-2在指定培养基中培养。采用免疫组化（IHC）和Western blotting检测SREBP 1的表达。MTT法和集落形成实验观察细胞增殖情况。采用免疫荧光、mRFP-GFP腺病毒载体和透射电镜观察自噬。我们使用链脲佐菌素（STZ）建立一个高糖小鼠模型，在体内study.ResultsWe发现，高血糖水平与胰腺癌患者预后不良。SREBP 1在胰腺癌组织和胰腺癌细胞系中均过表达。高糖微环境通过增强SREBP 1表达促进肿瘤增殖、抑制凋亡和抑制自噬水平。此外，自噬的激活加速了SREBP 1的表达并抑制了细胞凋亡。此外，高糖通过增强SREBP 1表达促进体内肿瘤生长。结论我们的研究结果表明，SREBP 1-自噬轴在高糖微环境诱导的肿瘤进展中起着至关重要的作用。SREBP 1可能是胰腺癌预防和治疗的新靶点。
BackgroundDiabetes is recognized to be a risk factor of pancreatic cancer, but the mechanism has not been fully elucidated. Sterol regulatory element binding protein 1 (SREBP1) is an important transcription factor involved in both lipid metabolism and tumor progression. However, the relationship between high glucose microenvironment, SREBP1 and pancreatic cancer remains to be explored.MethodsClinical data and surgical specimens were collected. Pancreatic cancer cell lines BxPc-3 and MiaPaCa-2 were cultured in specified medium. Immunohistochemistry (IHC) and western blotting were performed to detect the expression of SREBP1. MTT and colony formation assays were applied to investigate cell proliferation. Immunofluorescence, mRFP-GFP adenoviral vector and transmission electron microscopy were performed to evaluate autophagy. We used streptozotocin (STZ) to establish a high glucose mouse model for the in vivo study.ResultsWe found that high blood glucose levels were associated with poor prognosis in pancreatic cancer patients. SREBP1 was overexpressed in both pancreatic cancer tissues and pancreatic cancer cell lines. High glucose microenvironment promoted tumor proliferation, suppressed apoptosis and inhibited autophagy level by enhancing SREBP1 expression. In addition, activation of autophagy accelerated SREBP1 expression and suppressed apoptosis. Moreover, high glucose promotes tumor growth in vivo by enhancing SREBP1 expression.ConclusionOur results indicate that SREBP1-autophagy axis plays a crucial role in tumor progression induced by high glucose microenvironment. SREBP1 may represent a novel target for pancreatic cancer prevention and treatment.