DJ-1, a novel biomarker and a selected target gene for overcoming chemoresistance in pancreatic cancer
DJ-1, a novel biomarker and a selected target gene for overcoming chemoresistance in pancreatic cancer
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DJ-1，一种新型生物标志物和克服胰腺癌化疗耐药性的选定靶基因
DOI：
10.1007/s00432-012-1205-3
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发表时间：
2012-09-01
影响因子：
3.6
通讯作者：
Wu, Yulian
中科院分区：
文献类型：
--
作者：
Chen, Ying;Kang, Muxing;Wu, Yulian
DJ-1的异常表达已被证明与许多肿瘤的发生有关。然而，它在胰腺癌中的作用尚不清楚。本研究的目的是探讨血清DJ-1是否可以作为胰腺癌潜在的生物标志物，并探讨DJ-1表达在吉西他滨诱导的胰腺癌化疗耐药中的生物学作用。为探讨DJ-1在胰腺癌化疗耐药中的作用，合成了靶向DJ-1的siRNA，构建了稳定表达DJ-1的细胞系。采用四甲基偶氮唑盐比色法、实时荧光定量聚合酶链式反应、Western印迹和流式细胞术等多种方法对肿瘤化疗耐药机制进行了研究。胰腺癌患者血清DJ-1水平明显高于正常对照组，并与胰腺癌的分化程度有关。DJ-1下调促进吉西他滨诱导三种胰腺癌细胞株的凋亡。相反，DJ-1的过表达降低了MIA Paca-2对吉西他滨诱导细胞凋亡的敏感性。我们的结果表明，DJ-1的血清水平可能是胰腺癌的一个潜在的生物标志物，并且DJ-1在胰腺癌的化疗耐药中起着关键作用，支持针对该癌基因的化疗方法的发展。
Aberrant expression of DJ-1 has been proven to be associated with tumorigenesis in many carcinomas. However, its role in pancreatic cancer is unknown. The aims of this study were to investigate whether the serum DJ-1 might be a potential biomarker for pancreatic cancer and to determine the biologic function of DJ-1 expression in gemcitabine-induced chemoresistance of pancreatic cancer.The serum level of DJ-1 was higher in 128 pancreatic cancer patients compared with 62 healthy controls by ELISA. To determine the effect of DJ-1 on pancreatic tumor chemoresistance, a siRNA-targeting DJ-1 was synthesized and a stably transfected cell line with DJ-1 over-expression was constructed. The mechanism of tumor chemoresistance was assessed by multiple methods, such as MTT assay, real-time PCR, Western blot and flow cytometry.The serum level of DJ-1 was higher in pancreatic cancer patients than healthy controls, and it has the relationship with tumor differentiation in pancreatic cancer. Down-regulation of DJ-1 enhanced gemcitabine-induced apoptosis in three pancreatic cancer cell lines. On the contrary, over-expression of DJ-1 desensitized the MIA PaCa-2 to the induction of apoptosis by gemcitabine.Our results suggest that the serum level of DJ-1 may be a potential biomarker for pancreatic cancer, and that DJ-1 plays critical roles in the pancreatic tumor chemoresistance, supporting the development of chemotherapeutic approaches targeting this oncogene.