H IF －1α促进卵巢癌贝伐单抗耐药的研究

HIF-1αinduces ovarian cancer to resistant to bevacizumab

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。

Objective To investigate the relationship between HIF-1αand bevacizumab resistant in o-vary cancer,and explore the influence on ovary cancer cell by HIF-1α.Methods The correlation was analyzed between HIF-1αexpression and clinicopathological parameters using immunohistochemistry in 62 patients with ovarian cancer.In addition,the expression of HIF-1αand VEGF were evaluated by real time PCR or Western Blot in SKOV3 and ES-2 cell under CoCl 2 treatment.Results HIF-1αwas 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-1αand VEGF,when compared to normal condition.Conclusion Our findings suggest that HIF-1αis associated with resistant to bevacizumab.It is more chemotherapeutic sensitivity when combined with bevacizumab and HIF-1αantibody.