Jnk signaling pathway-mediated regulation of Stat3 activation is linked to the development of doxorubicin resistance in cancer cell lines
Jnk signaling pathway-mediated regulation of Stat3 activation is linked to the development of doxorubicin resistance in cancer cell lines
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DOI：
10.1016/j.bcp.2009.09.008
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发表时间：
2010-02-01
影响因子：
5.8
通讯作者：
Yoon, Sungpil
中科院分区：
文献类型：
--
作者：
Kim, Ju-Hwa;Lee, Seok Chul;Yoon, Sungpil
我们试图确定改变的转录因子（Stat，AP 1和NF-kB）或信号蛋白（Erk 1/2，p38，Akt，Jnk，Jak和c-Src）在癌细胞系中的生长被阿霉素（DOX）治疗。JNK 1是唯一被激活的信号蛋白。DOX增加Stat 3磷酸化、核定位和转录活性。JNK 1激活似乎是Stat 3活性所必需的。通过JNK途径的Stat 3活性在来源于其他器官的其他细胞系中是保守的。在DOX处理后存活的细胞中，Stat 3的转录活性增加，表明Stat 3活化有助于对细胞毒性的抗性。为了更好地理解Stat 3在JNK 1活化中的作用，我们研究了其对DOX处理的细胞的活力的影响。DOX和JNK抑制剂的共同治疗与癌细胞的活力呈负相关，并降低了Stat 3活性。总之，这些结果表明，通过JNK途径激活Stat 3促进癌细胞对DOX的抗性。(C)2009 Elsevier Inc. All rights reserved.
We sought to identify altered transcription factors (Stat, AP1, and NF-kB) or signal proteins (Erk1/2, p38, Akt, Jnk, Jak, and c-Src) in cancer cell lines whose growth was arrested by doxorubicin (DOX) treatment. Jnk1 was the only signal protein to be activated. DOX increased Stat3 phosphorylation, nuclear localization, and transcriptional activity. Jnk1 activation appeared to be required for Stat3 activity. Stat3 activity via the Jnk pathway was conserved in other cell lines originating from other organs. Transcriptional activity of Stat3 was increased in cells surviving DOX treatment suggesting that Stat3 activation contributed to the resistance to cytotoxicity. To better understand the role of Stat3 in Jnk1 activation, we investigated its effect on the viability of DOX-treated cells. Co-treatment with DOX and Jnk inhibitor negatively correlated with the viability of cancer cells and reduced Stat3 activity. Taken together, these results indicate that Stat3 activation via the Jnk pathway promotes the resistance of cancer cells to DOX. (C) 2009 Elsevier Inc. All rights reserved.