FOXM1 modulates cisplatin sensitivity by regulating EXO1 in ovarian cancer

Cisplatin is commonly used in ovarian cancer chemotherapy, however, chemoresistance to cisplatin remains a great clinical challenge. Oncogenic transcriptional factor FOXM1 has been reported to be overexpressed in ovarian cancer. In this study, we aimed to investigate the potential role of FOXM1 in o...

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Bibliographic Details
Published in:PloS one 2014-05, Vol.9 (5), p.e96989
Main Authors: Zhou, Jinhua, Wang, Yunfei, Wang, You, Yin, Xia, He, Yifeng, Chen, Lilan, Wang, Wenwen, Liu, Ting, Di, Wen
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis - drug effects
Biology and life sciences
Breast cancer
Cancer
Cancer therapies
Cell cycle
Cell growth
Cell Line, Tumor
Chemoresistance
Chemotherapy
Cisplatin
Cisplatin - pharmacology
Cisplatin - therapeutic use
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
DNA Repair - drug effects
DNA Repair Enzymes - metabolism
Drug Resistance, Neoplasm
Education
Exodeoxyribonucleases - metabolism
Female
Forkhead Box Protein M1
Forkhead Transcription Factors - metabolism
Gene expression
Gynecology
Hospitals
Humans
Kinases
Laboratories
Medicine
Medicine and Health Sciences
Obstetrics
Oncology
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Ovary - drug effects
Ovary - metabolism
Ovary - pathology
Ribonucleic acid
RNA
Sensitivity
siRNA
Toxicity
Transcription factors
Up-Regulation
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Summary:Cisplatin is commonly used in ovarian cancer chemotherapy, however, chemoresistance to cisplatin remains a great clinical challenge. Oncogenic transcriptional factor FOXM1 has been reported to be overexpressed in ovarian cancer. In this study, we aimed to investigate the potential role of FOXM1 in ovarian cancers with chemoresistance to cisplatin. Our results indicate that FOXM1 is upregulated in chemoresistant ovarian cancer samples, and defends ovarian cancer cells against cytotoxicity of cisplatin. FOXM1 facilitates DNA repair through regulating direct transcriptional target EXO1 to protect ovarian cancer cells from cisplatin-mediated apoptosis. Attenuating FOXM1 and EXO1 expression by small interfering RNA, augments the chemotherapy efficacy against ovarian cancer. Our findings indicate that targeting FOXM1 and its target gene EXO1 could improve cisplatin effect in ovarian cancer, confirming their role in modulating cisplatin sensitivity.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0096989