Purpose

Pancreatic cancer is one of the most aggressive cancers. Preclinical and clinical data indicate that Notch 1 ligand jagged1 (JAG1) plays a pro-oncogenic role in several malignant cancers. As yet, however, the role of JAG1 in pancreatic cancer is poorly understood. The objective of the present study was to investigate JAG1 as a therapeutic target in human pancreatic cancer.

Methods

Expression levels of Notch signaling molecules were assessed using GEO datasets and Western blot analysis, respectively. Anti-tumor effects following JAG1 silencing were evaluated using in vitro and in vivo assays. Prognostic implications were assessed using GEO datasets.

Results

Using GEO datasets and Western blot analysis we detected significantly higher JAG1 mRNA and protein expression levels in pancreatic cancer compared to normal pancreatic tissues. JAG1 silencing significantly restrained the growth, migration and invasion of pancreatic cancer cells through the induction of apoptosis and blockade of various kinases independent of the Notch1 pathway. Combined JAG1 silencing and gemcitabine treatment showed synergistic anti-viability effects in human pancreatic cancer cells. JAG1 silencing also resulted in significant anti-cancer effects in vivo and high JAG1 expression was found to be associated with an adverse prognosis in pancreatic cancer patients.

Conclusions

From our data we conclude that JAG1 may be a promising therapeutic target in pancreatic cancer.

中文翻译：

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Jagged1表达与人类胰腺癌的恶性程度和预后的关系。

目的

胰腺癌是最具侵略性的癌症之一。临床前和临床数据表明，Notch 1配体jagged1（JAG1）在几种恶性肿瘤中起促癌作用。然而，迄今为止，人们对JAG1在胰腺癌中的作用了解甚少。本研究的目的是研究JAG1作为人类胰腺癌的治疗靶标。

方法

Notch信号分子的表达水平分别使用GEO数据集和Western blot分析进行评估。使用体外和体内试验评估JAG1沉默后的抗肿瘤作用。使用GEO数据集评估了预后意义。

结果

使用GEO数据集和Western印迹分析，与正常胰腺组织相比，我们在胰腺癌中检测到显着更高的JAG1 mRNA和蛋白质表达水平。JAG1沉默通过诱导凋亡和阻断各种与Notch1途径无关的激酶来显着抑制胰腺癌细胞的生长，迁移和侵袭。JAG1沉默和吉西他滨联合治疗在人胰腺癌细胞中显示出协同的抗生存力作用。JAG1沉默还导致体内显着的抗癌作用，并且发现高JAG1表达与胰腺癌患者的不良预后有关。

结论

根据我们的数据，我们得出结论，JAG1可能是胰腺癌有希望的治疗靶标。