Chen Yi-Fei, Wang Shu-Ying, Yang You-Hui, Zheng Jiang, Liu Ting, Wang Li
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, P.R. China.
Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.
Int J Mol Med. 2017 Jun;39(6):1564-1570. doi: 10.3892/ijmm.2017.2978. Epub 2017 May 8.
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.
晚期诊断以及缺乏特异性治疗靶点导致上皮性卵巢癌（EOC）患者生存率较低，EOC是最致命的妇科恶性肿瘤。因此，迫切需要筛选诊断标志物并确定治疗靶点。热休克因子1（HSF1）已被证明在某些恶性肿瘤中过度表达，并参与肿瘤的起始、发展、转化和转移。据信HSF1是抗肿瘤治疗的一个有前景的候选靶点。然而，其在卵巢癌中的表达模式和功能远未得到充分阐明。因此，我们检测了人EOC组织中HSF1的表达，并在异种移植肿瘤模型中评估了其促癌活性。使用卵巢组织印迹通过免疫组织化学分析检测人EOC组织中HSF1的表达。针对HSF1的特异性短发夹RNA（shRNA）用于敲低SKOV3细胞中的HSF1。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑（MTT）法评估细胞增殖活性；通过流式细胞术分析确定细胞周期分布和凋亡情况。在正常卵巢组织中，几乎检测不到HSF1，而在恶性EOC组织中发现HSF1高表达，包括浆液性、黏液性、子宫内膜样和透明细胞EOC组织。在HSF1敲低的SKOV3细胞中观察到增殖活性受到抑制且凋亡加剧。在裸鼠异种移植模型中，发现HSF1的下调导致致癌作用减弱，表明调节HSF1对EOC具有抗肿瘤作用。我们的研究结果表明，HSF1可能被视为人类EOC的潜在候选诊断标志物，并且调节HSF1可能是一种有前景的针对人类EOC的治疗策略。
