He Xiaojun, Zhang Hui, Xiao Mei, Kong Yalin, Li Wenbing, Zhang Hongyi
Department of Hepatobiliary Surgery, Air Force General Hospital of PLA, 30th Fucheng Road, Beijing, 100142, China,
Tumour Biol. 2015 May;36(5):3245-9. doi: 10.1007/s13277-014-2953-2. Epub 2014 Dec 18.
Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor with high lethality in humans. Pancreatic intraepithelial neoplasia (PanIN) is the predominant precancerous lesion for PDAC. Although PanIN is frequently detected in the normal and inflamed pancreas, only a few of PanIN eventually progress into PDAC. Thus, inhibition of PanIN-to-PDAC conversion is critical for preventing the occurrence of PDAC. Here, we evaluated the effect of inhibition of epidermal growth factor receptor (EGFR) signaling on the progression of low-grade PanIN into high-grade PDAC in an established mouse PDAC model (Ptf1a-Cre; K-rasG12D). We found that intraductal infusion of EGFR inhibitors at 12 weeks of age, which induced sustained inhibition of EGFR signaling in the pancreas, significantly decreased the incidence of high-grade PanIN in these mice at 24 weeks of age. Thus, our study suggests that inhibition of EGFR signaling may prevent development of PDAC.
胰腺导管腺癌（PDAC）是一种在人类中具有极高致死率的恶性肿瘤。胰腺上皮内瘤变（PanIN）是PDAC的主要癌前病变。尽管PanIN在正常和发炎的胰腺中经常被检测到，但只有少数PanIN最终会发展成PDAC。因此，抑制PanIN向PDAC的转化对于预防PDAC的发生至关重要。在此，我们在已建立的小鼠PDAC模型（Ptf1a-Cre；K-rasG12D）中评估了抑制表皮生长因子受体（EGFR）信号传导对低级别PanIN进展为高级别PDAC的影响。我们发现，在12周龄时经导管内注入EGFR抑制剂，可在胰腺中诱导EGFR信号的持续抑制，显著降低这些小鼠在24周龄时高级别PanIN的发生率。因此，我们的研究表明，抑制EGFR信号传导可能预防PDAC的发生。
