title: Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation.
abstract: Ovarian tumor is one of the most lethal gynecologic cancers, but differentiation therapy for this cancer is poorly characterized. Here, we show that thrichostatin A (TSA), the well known inhibitor of histone deacetylases (HDACs), can induce cell differentiation in HO8910 ovarian cancer cells. TSA-induced cell differentiation is characterized by typical morphological change, increased expression of the differentiation marker FOXA2, decreased expression of the pluripotency markers SOX2 and OCT4, suppressing cell proliferation, and cell cycle arrest in the G1 phase. TSA also induces an elevated expression of cell cycle inhibitory protein p21Cip1 along with a decrease in cell cycle regulatory protein cyclin D1. Significantly, blockage of epidermal growth factor receptor (EGFR) signaling pathway with specific inhibitors of this signaling cascade promotes the TSA-induced differentiation of HO8910 cells. These results imply that the EGFR cascade inhibitors in combination with TSA may represent a promising differentiation therapy strategy for ovarian cancer.
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Genbao
authors.initials: G
authors.lastname: Shao
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Lai
authors.affiliation: Department of Oncology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wan
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wei
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Liuping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Qixiang
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Department of Intensive Care Unit, The Affiliated Third People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212005, P.R. China.
authors.forename: Shengqiang
authors.initials: S
authors.lastname: Zou
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: D006877:Hydroxamic Acids; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; C012589:trichostatin A; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt