BNIP3在胰腺癌中的研究进展

Research advancement of BNIP3 on pancreatic cancer

胰腺癌的高度恶性表型与其凋亡异常有关。BNIP3,一种促凋亡蛋白,可通过与Bcl-2、Bcl-xl形成异构体而拮抗其抗凋亡的作用,也可诱导自体吞噬。缺氧,实体肿瘤中最常见的特征之一,可通过HIF-1α或非HIF-1α依赖途径诱导BNIP3的表达。BNIP3在乳腺癌、非小细胞肺癌和脑瘤中高表达,但在胰腺癌组织及细胞系中存在明显的低表达。BNIP3在胰腺癌中的低表达主要与BNIP3启动子的甲基化有关,也与S100A4等过表达有关。BNIP3的缺乏与胰腺癌对吉西他滨、5-FU的耐药有关,并可能与胰腺癌的预后差相关。BNIP3是一个新的胰腺癌治疗的靶点。

Highly malignant phenotype of pancreatic cancer is related to abnormal apoptosis. BNIP3, a pro-apoptosis protein, can heterodimerizate with Bcl-2 and Bcl-xL to reverse their anti-apoptosis function, and also can induce autophagy. The expression of BNIP3 can be induced by hypoxia, one of the most common features of solid tumors, by HIF-1α-dependent or independent pathway. Elevated expression of BNIP3 was seen in breast cancer, non-small cell lung cancer and glioblastoma tumors, but obvious low expression of BNIP3 was observed in pancreatic cancer tissues and pancreatic cancer cell lines. Low expression of BNIP3 in pancreatic cancer is at- tributed to its promoter hypermethylation or over-expression of S100A4, Absence of BNIP3 is associated with resistance to Gemcitabine, 5-fluorouracil, and may be associated with poor prognosis. BNIP3 may be a novel target for pancreatic cancer therapy.