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首页> 外文期刊>Journal of dermatological science >Novel GSK-3 kinase inhibitor Pym-5 induces GSK-3β rather than GSK-3α-dependent melanogenesis in murine melanoma cells
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Novel GSK-3 kinase inhibitor Pym-5 induces GSK-3β rather than GSK-3α-dependent melanogenesis in murine melanoma cells

机译：Novel GSK-3 kinase inhibitor Pym-5 induces GSK-3β rather than GSK-3α-dependent melanogenesis in murine melanoma cells

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? 2022 Japanese Society for Investigative DermatologyBackground: Glycogen synthase kinase-3 (GSK-3) inhibitors are considered to activate Wnt/β-Catenin, which remains a controversial topic in melanoma treatment. Objective: Here, we have developed Pym-5, an attractive GSK-3 inhibitor. Using Pym-5 as a chemical tool to probe the GSK-3 biology, we aimed to investigate the potential of GSK-3 inhibition as a strategy of melanoma treatment and underlying mechanisms. Methods: Using pigment B16 and B16BL6 murine melanoma model in vitro and a zebrafish pigmentation model in vivo, we investigated Pym-5-meditaed activation of Wnt/β-Catenin, melanogenesis and antitumor response in melanoma treatment. Results: We found that Pym-5 delayed the growth and promoted melanogenesis of melanoma cells. Pym-5 activated the transcription of β-Catenin and responsive targets genes (AXIN2 and MITF), melanin biosynthesis genes (TYR, TYRP1 and TYRP2) and eventually elevated the production of melanin. Interestingly, genetic inactivation of GSK-3β, but not its paralogue GSK-3α, compromised Pym-5-mediated melanogenesis in B16 and B16BL6 cells. Conclusion: These data provide insight into the potential therapeutic benefits obtained from activation of Wnt/β-Catenin signaling pathway and how Pym-5 can regulate melanin production and the rationale for future clinical application of GSK-3 inhibitor in melanoma patients.

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