{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:58:49Z","timestamp":1789563529943,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,24]],"date-time":"2017-07-24T00:00:00Z","timestamp":1500854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. Signal transducer and activator of transcription 3(STAT3) expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6). Therefore, this work was planned to investigate the role of STAT3 and examine the efficacy of a novel anti\u2010cancer compound \u2010HO\u20103867, which is an inhibitor of STAT3, using known OCCC cell lines. Results demonstrate that treatment with HO\u20103867 decreased expression of pSTAT3 Tyr705 as well pSTAT3 Ser727, while total STAT3 remained constant. STAT3 overexpression increased the migration capability in OVTOKO cells <jats:italic>in vitro<\/jats:italic> and led to an increased tumor size when injected <jats:italic>in vivo<\/jats:italic>. The inhibitory effect of HO\u20103867 on cell proliferation and cell survival was accompanied by increased apoptosis, within 24 h post treatment. Treatment with HO\u20103867 resulted in a decrease in Bcl\u20102 and increase of cleavage of caspase 3, caspase 7, and PARP, confirming induction of apoptosis after treatment with HO\u20103867. In addition, HO\u20103867 significantly inhibited formation of human umbilical vein endothelial cells capillary\u2010like structures and invasion at both 5 and 10 \u00b5M concentrations. STAT3 expression plays an important role in the spread of OCCC <jats:italic>in vitro<\/jats:italic> as well as <jats:italic>in vivo<\/jats:italic>. Thus, we can exploit the STAT3 pathway for targeted drug therapy. Inhibition of pSTAT3 using HO\u20103867in OCCC cell lines appears to be a promising therapy. This is of utmost importance given the poor response of OCCC to standard chemotherapy regimens.<\/jats:p>","DOI":"10.1002\/ijc.30847","type":"journal-article","created":{"date-parts":[[2017,6,24]],"date-time":"2017-06-24T08:34:36Z","timestamp":1498293276000},"page":"1856-1866","source":"Crossref","is-referenced-by-count":35,"title":["Targeting STAT3 by HO3867 induces apoptosis in ovarian clear cell carcinoma"],"prefix":"10.1002","volume":"141","author":[{"given":"Kristin","family":"Bixel","sequence":"first","affiliation":[{"name":"Division of Gynecologic Oncology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uksha","family":"Saini","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus 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