title: KLF4 expression enhances the efficacy of chemotherapy drugs in ovarian cancer cells.
abstract: KLF4 is a transcriptional factor that can function either as a tumor suppressor or oncogene in cancer based on its cellular context. We recently demonstrated that KLF4 was a tumor suppressor in ovarian cancer cells by inhibiting the epithelial to mesenchymal transition. Here we report that KLF4 expression was downregulated in ovarian cancer tissue compared to normal ovarian tissue, and low KLF4 expression correlated with high risk ovarian carcinoma and poor patient survival. Enforced KLF4 expression by lentiviral transduction sensitized ovarian cancer cells to the effects of the chemotherapy drugs, paclitaxel and cisplatin. Treatment of ovarian cancer cells with APTO-253, a small molecule inducer of KLF4, enhanced the efficacy of both chemotherapy drugs. KLF4 expression mediated by lentiviral vector or induced by APTO-253 resulted in G1 phase arrest in ovarian cancer cells. Our results demonstrate that for the first time that inducing KLF4 expression with APTO-253 is a novel therapeutic strategy for treating ovarian cancer.
authors.affiliation: The Third Affiliated Hospital, Zhengzhou University, PR China; Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Baojin
authors.initials: B
authors.lastname: Wang
authors.affiliation: The Third Affiliated Hospital, Zhengzhou University, PR China. Electronic address: shenairong08@163.com.
authors.forename: Airong
authors.initials: A
authors.lastname: Shen
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Ouyang
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Guannan
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA; Henan Agricultural University, PR China; Henan University of Animal Husbandry and Economy, PR China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Huo
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Chuanhe
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Women's Health Educational System, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan; Department of Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: dpx1cn@gmail.com.
authors.forename: Peixin
authors.initials: P
authors.lastname: Dong
authors.affiliation: Department of Women's Health Educational System, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan; Department of Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hidemichi
authors.initials: H
authors.lastname: Watari
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Pfeffer
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA; Center for Cancer Research, The University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address: jyue@uthsc.edu.
authors.forename: Junming
authors.initials: J
authors.lastname: Yue
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000819:agonists / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010618:Phenanthrolines / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C000608520:APTO-253; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007093:Imidazoles; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D010618:Phenanthrolines
keywords: APTO-253; Cell cycle; Chemoresistance; KLF4; Ovarian cancer