Jnk signaling pathway-mediated regulation of Stat3 activation is linked to the development of doxorubicin resistance in cancer cell lines

被引：60

作者：

Kim, Ju-Hwa ^{[1
]}

Lee, Seok Chul ^{[1
]}

Ro, Jungsil ^{[1
]}

Kang, Han Sung ^{[1
]}

Kim, Hyung Sik ^{[2
]}

Yoon, Sungpil ^{[1
]}

机构：

[1] Natl Canc Ctr, Res Inst, Goyang Si 411764, Gyeonggi Do, South Korea

[2] Pusan Natl Univ, Coll Pharm, Pusan, South Korea

来源：

BIOCHEMICAL PHARMACOLOGY | 2010年 / 79卷 / 03期

关键词：

Doxorubicin; Stat3; Jnk1; SP600125; DOX resistance; cancer; METASTATIC BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; PROTEIN-KINASES; TRANSCRIPTION; KAPPA-B; CHEMOTHERAPY; APOPTOSIS; INHIBITION; INDUCTION; SRC;

D O I：

10.1016/j.bcp.2009.09.008

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：373 / 380

页数：8

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