Insulin-Like Growth Factor 1 Receptor Promotes the Growth and Chemoresistance of Pancreatic Cancer
Insulin-Like Growth Factor 1 Receptor Promotes the Growth and Chemoresistance of Pancreatic Cancer
复制标题
胰岛素样生长因子1受体促进胰腺癌的生长和化疗耐药
DOI：
10.1007/s10620-013-2673-2
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发表时间：
2013-09-01
影响因子：
3.1
通讯作者：
Yang, Yinmo
中科院分区：
文献类型：
--
作者：
Tian, Xiaodong;Hao, Kun;Yang, Yinmo
背景胰岛素样生长因子1受体（IGF1R）在胰腺癌的进展中发挥重要作用。目的本研究旨在探讨IGF1R敲低对胰腺癌细胞增殖、凋亡和化疗敏感性的影响，并探讨其可能的机制。方法建立表达IGF1R shRNA的胰腺癌细胞，体外检测细胞增殖、集落形成以及对吉西他滨化疗敏感性。分别通过蛋白质印迹分析和荧光素酶测定检测AKT和NF-κB的激活。建立异种移植小鼠模型来评估IGF1R敲低的体内抗肿瘤作用。结果IGF1R敲低显着抑制胰腺癌细胞增殖和集落形成，诱导细胞凋亡，并抑制异种移植肿瘤生长。此外，IGF1R敲低显着增强了胰腺癌细胞对吉西他滨的化疗敏感性，这与PI3K/AKT和NF-κB通路的抑制有关。结论IGF1R敲低通过抑制PI3K/AKT和NF-κB通路抑制肿瘤生长并增强胰腺癌的化疗敏感性，是克服胰腺癌化疗耐药的一种有前景的方法。
BackgroundInsulin-like growth factor 1 receptor (IGF1R) plays important roles in the progression of pancreatic cancer. However, the underlying mechanism remains unclear.AimsThe purpose of this study was to investigate the effects of IGF1R knockdown on the proliferation, apoptosis and chemosensitivity of pancreatic cancer cells, and explore the possible mechanisms.MethodsPancreatic cancer cells expressing IGF1R shRNA were established, and the cell proliferation, colony formation, and chemosensitivity to gemcitabine were examined in vitro. The activation of AKT and NF-κB was detected by Western blot analysis and luciferase assay, respectively. Xenograft mice models were established to evaluate the in vivo anti-tumor effects of IGF1R knockdown.ResultsIGF1R knockdown notably inhibited pancreatic cancer cell proliferation and colony formation, induced apoptosis, and inhibited xenograft tumor growth. Moreover, IGF1R knockdown significantly enhanced chemosensitivity to gemcitabine in pancreatic cancer cells, and this was correlated with the inhibition of PI3K/AKT and NF-κB pathways.ConclusionsIGF1R knockdown suppresses tumor growth and enhances chemosensitivity in pancreatic cancer via the inhibition of PI3K/AKT and NF-κB pathways, and is a promising approach to overcome the chemoresistance of pancreatic cancer.