STAT3 as a target of molecular targeting therapy for oral cancer: Cell-based screening using inhibitor screening kits

Nagumo, Tatsuhito; Ito, Daisuke; Tsukamoto, Hikari; Yasuda, Arisa; Shintani, Satoru

doi:10.1016/j.ajoms.2011.06.007

Cited by 3 publications

(1 citation statement)

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“…JSI-124 also decreased expression of pSTAT3 expression as well as survivin, a downstream target of STAT3 signaling pathway. However, the in vivo antitumor efficacy of JSI-124 in OSCC has not been reported [27] . In nasopharyngeal cancer, administration of JSI-124 in nude mice before tumor cell inoculation suppressed in vivo tumor formation [28] .…”

Section: Discussionmentioning

confidence: 99%

JAK Kinase Inhibition Abrogates STAT3 Activation and Head and Neck Squamous Cell Carcinoma Tumor Growth

et al. 2015

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Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 has been implicated in cell proliferation and survival of many cancers including head and neck squamous cell carcinoma (HNSCC). AZD1480, an orally active pharmacologic inhibitor of JAK1/JAK2, has been tested in several cancer models. In the present study, the in vitro and in vivo effects of AZD1480 were evaluated in HNSCC preclinical models to test the potential use of JAK kinase inhibition for HNSCC therapy. AZD1480 treatment decreased HNSCC proliferation in HNSCC cell lines with half maximal effective concentration (EC50) values ranging from 0.9 to 4 μM in conjunction with reduction of pSTAT3Tyr705 expression. In vivo antitumor efficacy of AZD1480 was demonstrated in patient-derived xenograft (PDX) models derived from two independent HNSCC tumors. Oral administration of AZD1480 reduced tumor growth in conjunction with decreased pSTAT3Tyr705 expression that was observed in both PDX models. These findings suggest that the JAK1/2 inhibitors abrogate STAT3 signaling and may be effective in HNSCC treatment approaches.

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Section: Discussionmentioning

confidence: 99%