title: Effect of histone deacetylase inhibitors on cell apoptosis and expression of the tumor suppressor genes RUNX3 and ARHI in ovarian tumors.
abstract: The aim of this study was to investigate the expression of Runt box 3 (RUNX3) and aplasia Ras homolog member I (ARHI) in ovarian tumors, and the effects of histone deacetylase inhibitors (HDACIs) on the expression of these genes and the growth of ovarian cancer cells. The mRNA expression of the RUNX3 and ARHI genes in normal ovaries and ovarian tumors was determined using reverse transcription polymerase chain reaction (RT-PCR). The effects of HDACIs on RUNX3 and ARHI expression in four ovarian cancer cell lines (SKOV3, A2780, COC1 and OC3) were determined using RT-PCR and the MTT assay. The expression of RUNX3 and ARHI in normal ovarian cells was 86 and 100%, respectively. Although the two genes were downregulated in ovarian tumors, the extent of downregulation differed. The expression of RUNX3 and ARHI was correlated with the degree of tumor malignancy (P<0.05). ARHI was expressed in all four ovarian cancer cell lines, whereas RUNX3 was expressed only in the OC3 cell line. Treatment with HDACIs upregulated the expression of ARHI and RUNX3 in the SKOV3 cell line only. In A2780 cells, HDACIs upregulated ARHI expression only in the presence of trichostatin A (TSA) plus cisplatin. HDACIs induced significant apoptosis in ovarian cancer cells, which was inversely correlated with the concentration and duration of treatment (P<0.05). In conclusion, RUNX3 and ARHI were shown to be expressed in normal ovarian cells; however, their expression was downregulated or lost in ovarian tumor cells. The combined detection of ARHI and RUNX3 expression may offer improved prediction and monitoring of ovarian malignancies. HDACIs were revealed to inhibit the growth of ovarian tumor cells and may constitute a novel therapeutic option for ovarian tumors.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan, Shandong 250000, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Peishu
authors.initials: P
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Fuying
authors.initials: F
authors.lastname: Xue
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050677:Core Binding Factor Alpha 3 Subunit; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C469745:LDLRAP1 protein, human; D012333:RNA, Messenger; C493729:Runx3 protein, human; D025521:Tumor Suppressor Proteins; C012589:trichostatin A; D002945:Cisplatin