https://scholars.lib.ntu.edu.tw/handle/123456789/458576
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Ho C.-M. | en_US |
dc.contributor.author | Huang C.-J. | en_US |
dc.contributor.author | Huang S.-H. | en_US |
dc.contributor.author | Chang S.-F. | en_US |
dc.contributor.author | WEN-FANG CHENG | en_US |
dc.creator | Ho C.-M.;Huang C.-J.;Huang S.-H.;Chang S.-F.;Wen-Fang Cheng | - |
dc.date.accessioned | 2020-02-14T02:49:45Z | - |
dc.date.available | 2020-02-14T02:49:45Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 1471-2407 | - |
dc.identifier.uri | 2-s2.0-84946478339 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/458576 | - |
dc.description.abstract | Background: Methylation of HIN-1 is associated with poor outcomes in patients with ovarian clear cell carcinoma (OCCC), which is regarded to be an aggressive, chemo-resistant histological subtype. This study aimed to evaluate whether 5-aza-2-deoxycytidine (5-aza-2-dC) can reverse methylation of the HIN-1 gene to restore chemo-sensitivity of OCCC and the possible mechanism. Methods: In vitro flow cytometric analysis and evaluation of caspase-3/7 activity of paclitaxel-sensitive and resistant OCCC cell lines were performed. Methylation status and expression changes of HIN-1 in the OCCC cell lines treated with 5-aza-2-dC were evaluated, and immunohistochemical staining of HIN-1 in OCCC tissues was performed. In vivo tumor growth with or without 5-aza-2-dC treatment was analyzed, and Western blotting of AKT-mTOR signaling-related molecules was performed. Results: G2-M phase arrest was absent in paclitaxel-resistant OCCC cells after treatment with the cytotoxic drug. The caspase activities of the chemo-resistant OCCC cells were lower than those of the chemo-sensitive OCCC cells when treated with paclitaxel. Methylation of HIN-1 was noted in paclitaxel-resistant OCCC cell lines and cancerous tissues. 5-aza-2-dC reversed the methylation of HIN-1, re-activated the expression of HIN-1, and then suppressed the in vivo tumor growth of paclitaxel-resistant OCCC cells. Immunoblotting revealed that phospho-AKT473 and phospho-mTOR were significantly increased in HIN-1-methylated paclitaxel-resistant OCCC cell lines. However, the expressions of phospho-AKT at Ser473 and Thr308 and phospho-mTOR decreased in the OCCC cells with a high expression of HIN-1. Conclusions: Demethylating agents can restore the HIN-1 expression in paclitaxel-resistant OCCC cells through the HIN-1-AKT-mTOR signaling pathway to inhibit tumor growth. ? 2015 Ho et al. | - |
dc.relation.ispartof | BMC Cancer | - |
dc.subject | 5-aza-2-deoxycytidine; AKT/mTOR; HIN-1; Hypoxia-inducing factor; Ovarian clear cell carcinoma | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | caspase 3; caspase 7; decitabine; mammalian target of rapamycin; paclitaxel; protein kinase B; serine; threonine; antineoplastic agent; cytokine; MTOR protein, human; paclitaxel; protein kinase B; SCGB3A1 protein, human; target of rapamycin kinase; tumor suppressor protein; adult; aged; animal experiment; animal model; Article; cancer inhibition; cancer resistance; clear cell carcinoma; clinical article; demethylation; drug effect; enzyme activity; ES2 cell line; female; flow cytometry; G2 phase cell cycle checkpoint; gene; gene expression; HIN 1 gene; human; human cell; human tissue; immunoblotting; immunohistochemistry; in vitro study; in vivo study; mouse; nonhuman; ovarian cancer cell line; ovarian clear cell carcinoma; ovary carcinoma; protein phosphorylation; signal transduction; TOV21G cell line; tumor growth; Western blotting; Adenocarcinoma, Clear Cell; animal; biosynthesis; DNA methylation; drug effects; drug resistance; metabolism; middle aged; nonobese diabetic mouse; Ovarian Neoplasms; physiology; SCID mouse; tumor cell line; Adenocarcinoma, Clear Cell; Adult; Aged; Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cytokines; DNA Methylation; Drug Resistance, Neoplasm; Female; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Middle Aged; Ovarian Neoplasms; Paclitaxel; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Suppressor Proteins | - |
dc.title | Demethylation of HIN-1 reverses paclitaxel-resistance of ovarian clear cell carcinoma through the AKT-mTOR signaling pathway | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1186/s12885-015-1744-5 | - |
dc.identifier.scopus | 56601533000 | - |
dc.relation.journalvolume | 15 | - |
dc.relation.journalissue | 1 | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
crisitem.author.dept | Obstetrics & Gynecology | - |
crisitem.author.dept | Obstetrics & Gynecology-NTUH | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Surgery-NTUCC | - |
crisitem.author.orcid | 0000-0002-3282-6304 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
顯示於: | 醫學系 |
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