Combined effects of EGFR and Hedgehog signaling pathway inhibition on the proliferation and apoptosis of pancreatic cancer cells
Combined effects of EGFR and Hedgehog signaling pathway inhibition on the proliferation and apoptosis of pancreatic cancer cells
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EGFR和hedgehog信号通路抑制联合作用对胰腺癌细胞增殖和凋亡的影响
DOI：
10.3892/or.2012.1808
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发表时间：
2012-08-01
期刊：
影响因子：
4.2
通讯作者：
Yang, Yin-Mo
中科院分区：
文献类型：
--
作者：
Qin, Chang-Fu;Hao, Kun;Yang, Yin-Mo
在本研究中，我们建立了一个新的实验模型，以研究RNAi靶向EGFR的影响，以及刺猬（HH）和EGFR信号通路对胰腺癌细胞增殖和凋亡的协同作用。建立了三种表达EGFR shRNA的人胰腺癌细胞系，并使用RT-PCR和Western印迹分析在这些线中评估了基因表达抑制。 EGFR RNAi和HH抑制对细胞增殖和凋亡的影响在体外和体内探索。我们观察到EGFR RNAi明显抑制了细胞的增殖和菌落形成，诱导的凋亡并显着降低了异种移植肿瘤的生长。此外，EGFR RNAi在体外和体内都显着增强了环胺敏感性，并且观察到AKT和ERK磷酸化的协同降低。本研究表明，对EGFR和HH信号传导途径的联合抑制可能比单独抑制每种方法更有前途的抗肿瘤方法，并且可能对HH和EGFR信号通路对ERK和AKT磷酸化具有协同作用。
In the present study, we established a new experimental model to investigate the effects of EGFR targeting by RNAi, and the synergistic actions between the Hedgehog (Hh) and EGFR signaling pathways on the proliferation and apoptosis in pancreatic cancer cells. Three human pancreatic cancer cell lines expressing EGFR shRNA were established, and gene expression inhibition was assessed in these lines using RT-PCR and western blot analysis. The effects of EGFR RNAi and Hh inhibition on cell proliferation and apoptosis were explored in vitro and in vivo. We observed that EGFR RNAi notably inhibited cell proliferation and colony formation, induced apoptosis and markedly decreased xenograft tumor growth. Furthermore, EGFR RNAi significantly enhanced cyclopamine sensitivity both in vitro and in vivo, and a synergistic decrease of both AKT and ERK phosphorylation was observed. The present study demonstrates that combined inhibition of both EGFR and Hh signaling pathways could establish a more promising antitumor approach than inhibiting each singly, and that there is a possible synergistic effect for Hh and EGFR signaling pathways on ERK and AKT phosphorylation.