NSC 74859 enhances doxorubicin cytotoxicity via inhibition of epithelial-mesenchyrnal transition in hepatocellular carcinoma cells

被引：35

作者：

Hu, Qi-Da ^{[1
]}

Chen, Wei ^{[1
]}

Yan, Tian-Lian ^{[2
]}

Ma, Tao ^{[1
]}

Chen, Cong-Lin ^{[1
]}

Liang, Chao ^{[1
]}

Zhang, Qi ^{[1
]}

Xia, Xue-Feng ^{[1
]}

Liu, Hao ^{[1
]}

Zhi, Xiao ^{[1
]}

Zheng, Xiao-Xiao ^{[1
]}

Bai, Xue-Li ^{[1
]}

Yu, Xia-Zhen ^{[1
]}

Liang, Ting-Bo ^{[1
]}

机构：

[1] Zhejiang Univ, Sch Med, Dept Hepatobiliary & Pancreat Surg, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China

[2] Zhejiang Univ, Sch Med, Dept Gastroenterol, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China

来源：

CANCER LETTERS | 2012年 / 325卷 / 02期

基金：

国家杰出青年科学基金;

关键词：

Hepatocellular carcinoma; Signal transducer and activator of transcription 3; Epithelial-mesenchymal transition; Doxorubicin; NSC; 74859; BREAST-CANCER CELLS; ANTITUMOR-ACTIVITY; SYSTEMIC THERAPY; GENE-THERAPY; STAT3; CHEMOTHERAPY; ACTIVATION; LIVER; TRANSCRIPTION; HEPATOMA;

D O I：

10.1016/j.canlet.2012.07.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Doxorubicin-based therapy is not effective for the treatment of hepatocellular carcinomas (HCCs). which often undergo epithelial-mesenchymal transition (EMT) during tumor progression. Activation of signal transducer and activator of transcription 3 (STAT3) is associated with chemosensitivity and may contribute to EMT during HCC chemotherapy. Low doses of NSC 78459 (a novel STAT3 inhibitor) have little effect on HCC cell proliferation, but efficiently inhibit STAT3. HuH-7, Hep3B, and HepG2 cells, with epithelial phenotypes, show significantly enhanced doxorubicin cytotoxicity following co-treatment with NSC 74859, whereas mesenchymal SNU-449 cells show no such enhancement. NSC 74859 inhibits STAT3 activity and suppressed doxorubicin-induced EMT in epithelial HCC cells. siRNA-mediated STAT3 knockdown resulted in EMT inhibition, which led to attenuation of NSC 74859-mediated chemosensitivity. Our data indicate NSC 74859 co-administration enhances doxorubicin cytotoxicity by inhibiting STAT3 in epithelial HCC cells. STAT3 deactivation and associated EMT attenuation contribute to the synergistic anti-tumor effects of combined NSC 74859/doxorubicin therapy. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

引用

页码：207 / 213

页数：7

共 40 条

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