Targeting HSF1 leads to an antitumor effect in human epithelial ovarian cancer
Targeting HSF1 leads to an antitumor effect in human epithelial ovarian cancer
复制标题
靶向HSF1对人类上皮性卵巢癌具有抗肿瘤作用
DOI：
10.3892/ijmm.2017.2978
复制
发表时间：
2017-06-01
影响因子：
5.4
通讯作者：
Wang, Li
中科院分区：
文献类型：
--
作者：
Chen, Yi-Fei;Wang, Shu-Ying;Wang, Li
晚期诊断和缺乏特异性治疗靶点导致卵巢上皮性癌（EOC）患者生存率低，EOC是最致命的妇科恶性肿瘤。因此，筛选诊断标志物和确定治疗靶点是当务之急。热休克因子1（HSF 1）在某些恶性肿瘤中过度表达，并参与肿瘤的发生、发展、转化和转移。HSF 1被认为是一个有希望的抗肿瘤治疗的候选者。然而，其在卵巢癌中的表达模式和功能远未完全阐明。因此，我们检测了HSF1在人EOC组织中的表达，并在异种移植肿瘤模型中评估了其促癌活性。采用免疫组化方法检测卵巢上皮癌组织中HSF1的表达。利用针对HSF 1的特异性短发夹RNA（shRNA）敲减SKOV 3细胞中的HSF 1。MTT法检测细胞增殖活性，流式细胞仪检测细胞周期和凋亡情况。在正常卵巢组织中，HSF 1几乎不表达，而在恶性卵巢上皮性癌组织中，包括浆液性、粘液性、类浆液性和透明细胞性卵巢上皮性癌组织中，HSF 1高表达。HSF1基因敲低的SKOV3细胞增殖活性受到抑制，凋亡增强。在裸鼠异种移植物中，发现HSF1的下调导致癌细胞生成减少，表明通过调节HSF1对EOC诱导的抗肿瘤作用。我们的研究结果表明，HSF1可能被认为是一个潜在的候选人EOC的诊断标志物，和HSF1的调制可能是一个有前途的治疗策略对人类EOC。
Late diagnosis and lack of specific therapeutic targets contribute to the low survival rate of patients with epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. Therefore, the screening of diagnostic markers and the identification of therapeutic targets are urgently required. Heat shock factor 1 (HSF1) has been demonstrated to be overexpressed in certain malignancies and to be involved in tumor initiation, development, transformation and metastasis. It is believed that HSF1 is a promising candidate for antitumor therapy. However, its expression pattern and function in ovarian cancer are far from being fully elucidated. Therefore, we examined the HSF1 expression in human EOC tissues, and evaluated its carcinogenesis-promoting activity in a xenograft tumor model. Examination of HSF1 expression in human EOC tissues was performed by immunohistochemical assay using ovarian tissue blots. Specific short hairpin RNA (shRNA) against HSF1 was employed to knockdown HSF1 in SKOV3 cells. Cell proliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay; cell cycle distribution and apoptosis were determined by flow cytometric analysis. In normal ovarian tissues, HSF1 was barely detected, whereas, high expression of HSF1 was found in malignant EOC tissues, including serous, mucinous, endometrioid, and clear cell EOC tissues. Suppressed proliferative activity and intensified apoptosis were observed in HSF1-knockdown SKOV3 cells. In nude mouse xenografts, downregulation of HSF1 was found to cause reduced carinogenesis, indicating the antitumor effect induced by modulation of HSF1 against EOC. Our findings suggest that HSF1 may be considered as a potential candidate diagnostic marker of human EOC, and that modulation of HSF1 could be a promising therapeutic strategy against human EOC.