Brusatol inhibits growth and induces apoptosis in pancreatic cancer cells via JNK/p38 MAPK/NF-κb/Stat3/Bc1-2 signaling pathway
Brusatol inhibits growth and induces apoptosis in pancreatic cancer cells via JNK/p38 MAPK/NF-κb/Stat3/Bc1-2 signaling pathway
复制标题
Brusatol 通过 JNK/p38 MAPK/NF-kappa b/Stat3/Bc1-2 信号通路抑制胰腺癌细胞生长并诱导细胞凋亡
DOI：
10.1016/j.bbrc.2017.04.133
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发表时间：
2017-06-10
影响因子：
3.1
通讯作者：
Zhou, Mengtao
中科院分区：
文献类型：
--
作者：
Xiang, Yukai;Ye, Wen;Zhou, Mengtao
布鲁塞尔醇是从鸦胆子菌中分离出来的一种化合物，已被证明对多种人类恶性肿瘤具有抗癌作用。然而，鸦胆子醇在胰腺癌中的作用却鲜为人知。研究证明，鸦胆子醇通过下调Bcl2的表达水平，上调Bax、裂解的Caspase-3的表达水平，抑制PATU-8988和PANC-1细胞的生长并诱导其凋亡。我们发现，JNK、p38MAPK的激活和NF-kappab、STAT3的失活与潜在的促凋亡信号通路有关。但与SB203580一样，SP600125不仅能阻断鸦胆子醇对JNK的激活，而且还能逆转p38的激活和BCI-2的降低。此外，SP600125和SB203580还逆转了核因子-kappab和STAT3的失活。此外，BAY 11-7082和S3I-201对磷酸化STAT3和Bcl2表达的影响与灯盏花醇相似。综上所述，我们得出的结论是，在胰腺癌中，鸦胆子醇确实抑制生长并诱导细胞凋亡。推测灯盏花醇通过JNK/p38MAPK/NF-kappab/STAT3/Bc1-2信号通路发挥抗癌作用。(C)爱思唯尔公司出版的2017年。
Brusatol, isolated from brucea, has been proved to exhibit anticancer influence on various kind of human malignancies. However, the role that brusatol plays in pancreatic cancer is seldom known by the public. Through researches brusatol was proved to inhibit growth and induce apoptosis in both PATU-8988 and PANC-1 cells by decreasing the expression level of Bcl-2 and increasing the expression levels of Bax, Cleaved Caspase-3. Then we found the activation of the JNK, p38 MAPK and inactivation of the NF-kappa b, Stat3 are related with the potential pro-apoptotic signaling pathways. However, SP600125 could not only abrogated the JNK activation caused by brusatol, but also reverse the p38 activation and the decrease of BcI-2 as SB203580 did. Besides, SP600125 and SB203580 also reversed the inactivation of NF-kappa b and Stat3. Furthermore, BAY 11-7082 and S3I-201 indeed had the similar effect as brusatol had on the expression of Phospho-Stat3 and Bcl-2. To sum up, we came to a conclusion that in pancreatic cancer, brusatol do inhibit growth and induce apoptosis. And we inferred that brusatol illustrates anticancer attribution via JNK/p38 MAPK/NF-kappa b/Stat3/Bc1-2 signaling pathway. (C) 2017 Published by Elsevier Inc.