Noscapine sensitizes chemoresistant ovarian cancer cells to cisplatin through inhibition of HIF-1α

被引：54

作者：

Su, Wenjing ^{[2
,3
]}

Huang, Lei ^{[1
]}

Ao, Qilin ^{[2
,3
]}

Zhang, Qinghua ^{[1
]}

Tian, Xun ^{[1
]}

Fang, Yong ^{[4
]}

Lu, Yunping ^{[4
]}

机构：

[1] Cent Hosp Wuhan, Dept Obstet & Gynecol, Wuhan 430014, Hubei, Peoples R China

[2] Huazhong Univ Sci & Technol, Tongji Hosp, Inst Pathol, Wuhan 430030, Hubei, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathol, Wuhan 430030, Hubei, Peoples R China

[4] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Canc Biol Ctr, Wuhan 430030, Hubei, Peoples R China

来源：

CANCER LETTERS | 2011年 / 305卷 / 01期

基金：

美国国家科学基金会;

关键词：

Noscapine; HIF-1; alpha; Ovarian neoplasm; Cisplatin; Chemoresistance; HYPOXIA-INDUCED CHEMORESISTANCE; MEDIATED APOPTOSIS; INDUCIBLE FACTOR-1; DRUG-RESISTANCE; FACTOR; 1-ALPHA; IN-VITRO; PATHWAY; ANGIOGENESIS; LYMPHOMA; PROTEIN;

D O I：

10.1016/j.canlet.2011.02.031

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is closely related with chemoresistance of solid tumors. The purpose of this study was to investigate the ability of noscapine to inhibit HIF-1 alpha and sensitize ovarian cancer cells to cisplatin (DDP) under hypoxic conditions. Herein, we report that noscapine sensitized cobalt-induced chemoresistant ovarian cancer cells to DDP-induced apoptosis and inhibition of cell proliferation. Noscapine also promoted proteasome-mediated degradation of cobalt-stabilized HIF-1 alpha protein, with subsequent inhibition of HIF-1 transcriptional activity. These data establish noscapine as a small molecule inhibitor of HIF-1 alpha and provide an evidence for its combination with DDP in combating ovarian cancer chemoresistance. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：94 / 99

页数：6

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