title: Inactivation of transforming growth factor-β-activated kinase 1 promotes taxol efficacy in ovarian cancer cells.
abstract: Resistance to taxol represents a major obstacle for long-term remission in ovarian cancer. Transforming Growth Factor-β-Activated Kinase 1 (TAK1) is a critical component in immune response pathway. However, the role of TAK1 in the development of chemoresistance in ovarian cancer remains unknown. Here, we showed that in vitro, taxol-resistant cells expressed higher TAK1, and the ratio of p-TAK1/TAK1 positively associated with taxol resistance in ovarian cancer cells. Inactivation of TAK1 by inhibitor 5Z-7-oxozeaenol or gene knockdown sensitized taxol cytotoxicity in vitro, promoting cell apoptosis and mitosis arrest. Moreover, resistant cells were much more sensitive to the combined TAK1 inhibitor and taxol treatment than their parental counterparts. Using xenograft mouse model, we found that 5Z-7-oxozeaenol significantly enhanced taxol efficacy in vivo. Thus, targeting TAK1 pathway is a promising strategy to enhance taxol response in ovarian cancer treatment.
authors.affiliation: Department of Obstetrics and Gynaecology, Anhui Medical University, Hefei 230032, China; Department of Obstetrics and Gynaecology, Chaohu Hospital of Anhui Medical University, Chaohu 238000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Bo
authors.affiliation: Clinical laboratory, Chaohu Hospital of Anhui Medical University, Chaohu 238000, China.
authors.forename: Huchuan
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Obstetrics and Gynaecology, Chaohu Hospital of Anhui Medical University, Chaohu 238000, China.
authors.forename: Zhengxian
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Obstetrics and Gynaecology, Chaohu Hospital of Anhui Medical University, Chaohu 238000, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qun
authors.affiliation: Department of Obstetrics and Gynaecology, Anhui Medical University, Hefei 230032, China. Electronic address: caoyunxia6@126.com.
authors.forename: Caoyun
authors.initials: C
authors.lastname: Xia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D015025:Zearalenone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000008:administration & dosage; D000099151:MAP Kinase Kinase Kinase 7; D007783:Lactones; D012118:Resorcinols
chemical_list: D020930:MAP Kinase Kinase Kinases; D017239:Paclitaxel; D015025:Zearalenone; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols
keywords: 5Z-7-oxozeaenol; Ovarian cancer; TAK1; Taxol