Department of General Surgery, Peking University First Hospital, Beijing 100034, PR China.
Oncol Rep. 2012 Aug;28(2):519-26. doi: 10.3892/or.2012.1808. Epub 2012 May 9.
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.
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 以及 Hedgehog（Hh）和 EGFR 信号通路之间的协同作用对胰腺癌细胞增殖和凋亡的影响。建立了三个表达 EGFR shRNA 的人胰腺癌细胞系，并通过 RT-PCR 和 Western blot 分析评估这些系中基因表达的抑制情况。在体外和体内探索了 EGFR RNAi 和 Hh 抑制对细胞增殖和凋亡的影响。我们观察到 EGFR RNAi 显著抑制细胞增殖和集落形成，诱导细胞凋亡并显著降低异种移植肿瘤生长。此外，EGFR RNAi 显著增强了体外和体内的环巴胺敏感性，并且观察到 AKT 和 ERK 磷酸化的协同降低。本研究表明，联合抑制 EGFR 和 Hh 信号通路可能比单独抑制每条通路建立更有前途的抗肿瘤方法，并且 Hh 和 EGFR 信号通路对 ERK 和 AKT 磷酸化可能存在协同作用。
