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Inhibition of tumor growth and angiogenesis of tamoxifen-resistant breast cancer cells by ruxolitinib, a selective JAK2 inhibitor
DC Field | Value | Language |
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dc.contributor.author | Kim, Ji Won | - |
dc.contributor.author | Gautam, Jaya | - |
dc.contributor.author | Kim, Ji Eun | - |
dc.contributor.author | Kim, Jung-Ae | - |
dc.contributor.author | Kang, Keon Wook | - |
dc.creator | 강건욱 | - |
dc.date.accessioned | 2019-06-25T07:39:23Z | - |
dc.date.available | 2020-04-05T07:39:23Z | - |
dc.date.created | 2019-10-24 | - |
dc.date.issued | 2019-04 | - |
dc.identifier.citation | Oncology Letters, Vol.17 No.4, pp.3981-3989 | - |
dc.identifier.issn | 1792-1074 | - |
dc.identifier.uri | https://hdl.handle.net/10371/154300 | - |
dc.description.abstract | Tamoxifen (TAM) is the most widely used treatment for estrogen receptor-positive breast cancer patients. Unfortunately, the majority of these patients exhibit TAM resistance following treatment. We previously reported that proliferation and migration were greater in TAM-resistant MCF-7 (TAMR-MCF-7) cells than in parental MCF-7 cells. Janus kinases (JAKs) are cytosolic tyrosine kinases that transduce signals from plasma membrane cytokines and growth factor receptors. JAK2 selectively phosphorylates signal transducer and activator of transcription (STAT)-3, and the JAK2-STAT3 signaling pathway is known as a crucial signaling pathway for the regulation of cancer progression and metastasis. In the present study, basal phosphorylation of STAT3 was revealed to be greater in TAMR-MCF-7 cells than in control MCF-7 cells. Ruxolitinib, a potent JAK2 inhibitor, was demonstrated to attenuate STAT3 phosphorylation and the proliferation of TAMR-MCF-7 cells. Ruxolitinib also suppressed the enhanced cell migration of TAMR-MCF-7 cells through the inhibition of epithelial mesenchymal transition. Vascular endothelial growth factor (VEGF), a representative target gene of the JAK2-STAT3 pathway, functions as a key regulator of invasion and angiogenesis. Ruxolitinib significantly inhibited VEGF mRNA expression and transcriptional activity. The present study also performed a chick embryo chorioallantoic membrane assay to assess tumor growth and angiogenesis in TAMR-MCF-7 cells. Ruxolitinib reduced tumor weight and the number of blood vessels produced by TAMR-MCF-7 cells in a concentration-dependent manner. These results indicated that JAK2 could be a new therapeutic target for TAM-resistant breast cancer. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | en |
dc.publisher | Spandidos Publications | - |
dc.title | Inhibition of tumor growth and angiogenesis of tamoxifen-resistant breast cancer cells by ruxolitinib, a selective JAK2 inhibitor | - |
dc.type | Article | - |
dc.identifier.doi | 10.3892/ol.2019.10059 | - |
dc.citation.journaltitle | Oncology Letters | - |
dc.identifier.wosid | 000462644700043 | - |
dc.identifier.scopusid | 2-s2.0-85063432734 | - |
dc.description.srnd | OAIID:RECH_ACHV_DSTSH_NO:T201905080 | - |
dc.description.srnd | RECH_ACHV_FG:RR00200001 | - |
dc.description.srnd | ADJUST_YN: | - |
dc.description.srnd | EMP_ID:A078837 | - |
dc.description.srnd | CITE_RATE:1.664 | - |
dc.description.srnd | DEPT_NM:약학과 | - |
dc.description.srnd | EMAIL:kwkang@snu.ac.kr | - |
dc.description.srnd | SCOPUS_YN:Y | - |
dc.citation.endpage | 3989 | - |
dc.citation.number | 4 | - |
dc.citation.startpage | 3981 | - |
dc.citation.volume | 17 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kang, Keon Wook | - |
dc.identifier.srnd | T201905080 | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | EPITHELIAL-MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | SIGNAL TRANSDUCER | - |
dc.subject.keywordPlus | MOLECULAR TARGETS | - |
dc.subject.keywordPlus | JAK1/2 INHIBITOR | - |
dc.subject.keywordPlus | GASTRIC-CANCER | - |
dc.subject.keywordPlus | PHASE-II | - |
dc.subject.keywordPlus | STAT3 | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | STRATEGIES | - |
dc.subject.keywordAuthor | ruxolitinib | - |
dc.subject.keywordAuthor | JAK2 | - |
dc.subject.keywordAuthor | STAT3 | - |
dc.subject.keywordAuthor | tamoxifen-resistant breast cancer | - |
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