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首页> 外文OA文献 >MPT0B098, a microtubule inhibitor, suppresses JAK2/STAT3 signaling pathway through modulation of SOCS3 stability in oral squamous cell carcinoma
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MPT0B098, a microtubule inhibitor, suppresses JAK2/STAT3 signaling pathway through modulation of SOCS3 stability in oral squamous cell carcinoma

机译：MPT0B098，微管抑制剂，通过调节口腔鳞状细胞癌中SOCS3的稳定性抑制JAK2 / STAT3信号通路

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[[abstract]]Microtubule inhibitors have been shown to inhibit Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signal transduction pathway in various cancer cells. However, little is known of the mechanism by which the microtubule inhibitors inhibit STAT3 activity. In the present study, we examined the effect of a novel small-molecule microtubule inhibitor, MPT0B098, on STAT3 signaling in oral squamous cell carcinoma (OSCC). Treatment of various OSCC cells with MPT0B098 induced growth inhibition, cell cycle arrest and apoptosis, as well as increased the protein level of SOCS3. The accumulation of SOCS3 protein enhanced its binding to JAK2 and TYK2 which facilitated the ubiquitination and degradation of JAK2 and TYK2, resulting in a loss of STAT3 activity. The inhibition of STAT3 activity led to sensitization of OSCC cells to MPT0B098 cytotoxicity, indicating that STAT3 is a key mediator of drug resistance in oral carcinogenesis. Moreover, the combination of MPT0B098 with the clinical drug cisplatin or 5-FU significantly augmented growth inhibition and apoptosis in OSCC cells. Taken together, our results provide a novel mechanism for the action of MPT0B098 in which the JAK2/STAT3 signaling pathway is suppressed through the modulation of SOCS3 protein level. The findings also provide a promising combinational therapy of MPT0B098 for OSCC.
机译：[[摘要]]已显示微管抑制剂可抑制各种癌细胞中的Janus激酶2 /信号转导和转录激活因子3（JAK2 / STAT3）信号转导途径。然而，关于微管抑制剂抑制STAT3活性的机理还知之甚少。在本研究中，我们研究了新型小分子微管抑制剂MPT0B098对口腔鳞状细胞癌（OSCC）中STAT3信号的影响。用MPT0B098处理各种OSCC细胞可诱导生长抑制，细胞周期停滞和凋亡，并增加SOCS3的蛋白水平。 SOCS3蛋白的积累增强了其与JAK2和TYK2的结合，从而促进JAK2和TYK2的泛素化和降解，从而导致STAT3活性降低。 STAT3活性的抑制导致OSCC细胞对MPT0B098细胞毒性致敏，这表明STAT3是口腔癌发生过程中耐药性的关键介体。此外，MPT0B098与临床药物顺铂或5-FU的组合可显着增强OSCC细胞的生长抑制和凋亡。综上所述，我们的结果为MPT0B098的作用提供了一种新的机制，其中JAK2 / STAT3信号通路通过调节SOCS3蛋白水平而受到抑制。该发现还提供了MPT0B098用于OSCC的有希望的组合疗法。

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    Peng, HY;

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  • 年度 2016
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