Targeting HSF1 leads to an antitumor effect in human epithelial ovarian cancer

Chen,Yi-Fei; Wang,Shu-Ying; Yang,You-Hui; Zheng,Jiang; Liu,Ting; Wang,Li

doi:10.3892/ijmm.2017.2978

Targeting HSF1 leads to an antitumor effect in human epithelial ovarian cancer

Authors:
- Yi-Fei Chen
- Shu-Ying Wang
- You-Hui Yang
- Jiang Zheng
- Ting Liu
- Li Wang
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Affiliations: 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
Published online on: May 8, 2017 https://doi.org/10.3892/ijmm.2017.2978
Pages: 1564-1570

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Abstract

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.

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