HIF-1α促进卵巢癌贝伐单抗耐药的研究

doi:10.11904/j.issn.1002-3070.2015.04.002

实用肿瘤学杂志 ›› 2015, Vol. 29 ›› Issue (4): 294-298.doi: 10.11904/j.issn.1002-3070.2015.04.002

HIF-1α促进卵巢癌贝伐单抗耐药的研究

于歌¹ ,杨先² ,刘晓东³ ,邵华¹ ,赵玉兰¹ ,王晶¹

1.哈尔滨医科大学附属肿瘤医院;
2.哈尔滨医科大学附属第四医院;
3.哈尔滨医科大学附属第二医院

收稿日期:2015-05-17 出版日期:2015-08-27 发布日期:2015-08-27
通讯作者: 王晶 E-mail:wj6507@126.com
作者简介:于歌,女,(1985-),硕士,主治医师,从事妇科肿瘤的研究
基金资助:
黑龙江省教育厅科学技术研究项目(12531217)

HIF-1α induces ovarian cancer to resistant to bevacizumab

YU Ge¹,YANG Xian²,LIU Xiaodong³,SHAO Hua¹,ZHAO Yulan¹,WANG Jing¹

1.The Affiliate Tumor Hospital of Harbin Medical University,Harbin 150081,China;
2.The Fourth Affiliated Hospital of Harbin Medical University;
3.The Second Affiliated Hospital of Harbin Medical University

Received:2015-05-17 Online:2015-08-27 Published:2015-08-27

摘要/Abstract

摘要： 目的分析卵巢癌患者中缺氧诱导因子-1α(Hypoxia inducible factor-1α,HIF-1α)的表达与贝伐单抗耐药的关系,研究HIF-1α对卵巢癌细胞的影响。方法收集62例术后应用贝伐单抗治疗的卵巢癌患者的癌组织样本,并对HIF-1α进行免疫组化评估,分析HIF-1α与贝伐单抗耐药的关系。氯化钴诱导卵巢癌细胞SKOV3和ES-2后应用Realtime-PCR和Western blot分析HIF-1α和血管内皮生长因子(Vascular endothelial growth factor,VEGF)的表达情况。结果 HIF-1α在卵巢癌组织高表达,与患者的血清CA125(P=0.027)和贝伐单抗耐药(P＜0.001)相关。低氧诱导SKOV3和ES-2卵巢癌细胞HIF-1α和VEGF表达明显增高。结论卵巢癌中HIF-1α与贝伐单抗耐药相关,联合使用贝伐单抗和抗HIF-1α药物,可以增强化疗敏感性。

关键词: 贝伐单抗, HIF-1α, 卵巢癌

Abstract: Objective To investigate the relationship between HIF-1α and bevacizumab resistant in ovary cancer,and explore the influence on ovary cancer cell by HIF-1α.Methods The correlation was analyzed between HIF-1α expression and clinicopathological parameters using immunohistochemistry in 62 patients with ovarian cancer.In addition,the expression of HIF-1α and VEGF were evaluated by real time PCR or Western Blot in SKOV3 and ES-2 cell under CoCl 2 treatment.Results HIF-1α was overexpressed in cancer tissue,and its high levels were related to CA125(P=0.027)and resistant to bevacizumab(P＜0.001).Moreover,CoCl2 could induce high expressions of HIF-1α and VEGF,when compared to normal condition.Conclusion Our findings suggest that HIF-1α is associated with resistant to bevacizumab.It is more chemotherapeutic sensitivity when combined with bevacizumab and HIF-1α antibody.

Key words: Bevacizumab, HIF-1α, Ovarian cancer

中图分类号:

R734.2

于歌,杨先,刘晓东,邵华,赵玉兰,王晶. HIF-1α促进卵巢癌贝伐单抗耐药的研究[J]. 实用肿瘤学杂志, 2015, 29(4): 294-298.

YU Ge,YANG Xian,LIU Xiaodong,SHAO Hua,ZHAO Yulan,WANG Jing. HIF-1α induces ovarian cancer to resistant to bevacizumab[J]. PRACTICAL ONCOLOGY JOURNAL, 2015, 29(4): 294-298.

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HIF-1α促进卵巢癌贝伐单抗耐药的研究

HIF-1α induces ovarian cancer to resistant to bevacizumab

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