Notch1 Contributes to Chemoresistance to Gemcitabine and Serves as an Unfavorable Prognostic Indicator in Pancreatic Cancer
Notch1 Contributes to Chemoresistance to Gemcitabine and Serves as an Unfavorable Prognostic Indicator in Pancreatic Cancer
复制标题
Notch1 有助于吉西他滨的化疗耐药性，并作为胰腺癌的不利预后指标
DOI：
10.1007/s00268-013-2010-0
复制
发表时间：
2013-07-01
影响因子：
2.6
通讯作者：
Shu, Hong
中科院分区：
文献类型：
--
作者：
Du, Xiao;Zhao, Yu-Pei;Shu, Hong
胰腺癌（PC）具有频繁的化疗耐药性和极差的预后。其潜在机制仍有待进一步阐明。为了探讨Notch 1在前列腺癌吉西他滨耐药中的作用及其预后意义，将特异性靶向Notch 1的小干扰RNA（siRNA）瞬时转染3种前列腺癌细胞系（AsPC-1、BxPC-3和MIA PaCa-2），检测其对吉西他滨的化疗敏感性。另一方面，Notch 1的表达进行了化学评价，并与临床病理和预后变量。成功敲除Notch 1的特异性siRNA诱导增加化疗敏感性吉西他滨在所有三个细胞系。免疫组化结果显示Notch 1在PC组织中的阳性表达率为54.8%，而在癌旁组织中的阳性表达率为16.4%。此外，Notch 1阳性与早期转移和总生存期缩短显著相关。多因素考克斯回归分析显示，Notch 1是影响PC预后的独立因素，Notch 1与吉西他滨耐药有关，是PC预后不良的重要指标。
Pancreatic cancer (PC) carries frequent chemoresistance and extremely dismal prognosis. The underlying mechanisms remain to be further elucidated. We here report the role of Notch1 in gemcitabine resistance and its prognostic significance in PC.A small interfering RNA (siRNA) specifically targeting Notch1 was transiently transfected into three PC cell lines (AsPC-1, BxPC-3, and MIA PaCa-2), followed by examination of chemosensitivity to gemcitabine. On the other hand, Notch1 expression was evaluated immunohistochemically and correlated with clinicopathological and prognostic variables.Successful knockdown of Notch1 by specific siRNA induced increased chemosensitivity to gemcitabine in all three cell lines. Immunohistochemical staining revealed that Notch1 was highly expressed in PC tissues (54.8 %), in contrast to that in para-tumor tissues (16.4 %). In addition, Notch1 positivity was significantly correlated with early-term metastasis and shortened overall survival. Multivariate Cox regression identified Notch1 as an independent prognostic factor.Notch1 contributes to chemoresistance to gemcitabine, and serves as a significant indicator of unfavorable prognosis in PC.