Combined anti-tumor effects of IFN-α and sorafenib on hepatocellular carcinoma in vitro and in vivo

被引：33

作者：

Wang, Lijing ^{[1
]}

Jia, Dongwei ^{[1
]}

Duan, Fangfang ^{[2
]}

Sun, Zhichao ^{[1
]}

Liu, Xiaojuan ^{[1
]}

Zhou, Lei ^{[1
]}

Sun, Linlin ^{[1
]}

Ren, Shifang ^{[1
]}

Ruan, Yuanyuan ^{[1
]}

Gu, Jianxin ^{[1
,2
]}

机构：

[1] Fudan Univ, Ctr Gene Res, Shanghai Med Coll, Shanghai 200032, Peoples R China

[2] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2012年 / 422卷 / 04期

关键词：

Hepatocellular carcinoma; Interferon-alpha; Sorafenib; Combination therapy; PHASE-II TRIAL; INTERFERON-ALPHA; RAF/MEK/ERK PATHWAY; INDUCED APOPTOSIS; C-MYC; GROWTH; THERAPY; CELLS; PROGRESSION; INHIBITION;

D O I：

10.1016/j.bbrc.2012.05.056

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hepatocellular carcinoma (HCC) is among the most common and aggressive cancers worldwide, and novel therapeutic strategies are urgently required to improve clinical outcome. Interferon-alpha (IFN-alpha) and sorafenib are widely used as anti-tumor agents against various malignancies. In this study, we investigated the combined effects of IFN-alpha and sorafenib against HCC. We demonstrated that the combination therapy synergistically suppressed HCC cellular viability; arrested cell cycle propagation and induced apoptosis in HCC cells. Further research revealed that IFN-alpha and sorafenib collaboratively regulated the expression levels of cell cycle-related proteins Cyclin A and Cyclin B as well as the pro-survival Bcl-2 family proteins Mcl-1, Bcl-2 and Bcl-X-L. Moreover, sorafenib inhibited IFN-alpha induced oncogenic signaling of STAT3, AKT and ERK but not the activation of the tumor suppressor STAT1. Xenograft experiments also confirmed the combined effects of IFN-alpha and sorafenib on tumor growth inhibition and apoptosis induction in vivo. In conclusion, these results provide rationale for the clinical application of IFN-alpha and sorafenib combination therapy in HCC treatment. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：687 / 692

页数：6

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