目的 研究秦皮素对人黑色素瘤A375细胞的增殖、迁移、侵袭的影响及其作用机制。方法 A375细胞给予秦皮素和核糖体S6蛋白激酶（ribosome S6 protein kinase，P70S6K）抑制剂PF-4708671进行干预，采用细胞计数法考察秦皮素和PF-4708671对A375细胞增殖能力的影响；采用Western blotting法检测秦皮素和PF-4708671对mTORC1/p70S6K/S6通路关键蛋白及上皮-间充质转化（epithelial-mesenchymal transition，EMT）相关蛋白表达的影响；采用细胞划痕实验和Transwell实验考察秦皮素和PF-4708671对A375细胞迁移和侵袭的影响。结果 秦皮素与PF-4708671均可显著抑制A375细胞的增殖、迁移和侵袭（P<0.05、0.01）。秦皮素与PF-4708671均显著抑制p70S6K/S6通路活性，下调间质细胞标志蛋白和基质金属蛋白酶（matrix metalloproteinases，MMP）表达水平（P<0.05、0.01）。结论 秦皮素可能通过下调p70S6K抑制A375细胞的增殖、迁移与侵袭。

Objective To study the effect and mechanism of fraxetin on proliferation, migration and invasion of human melanoma A375 cells. Methods A375 cells were treated with fraxetin and ribosomal S6 protein kinase (P70S6K) inhibitor PF-4708671 for intervention, the effect of fraxetin and PF-4708671 on proliferation of A375 cells was measured by cell counting. Western blotting was used to detect the effect of fraxetin and PF-4708671 on expressions of mTORC1/p70S6K/S6 signaling pathway key proteins and epithelial-mesenchymal transition (EMT) related proteins in A375 cells. Wound healing assay and Transwell assay were used to detect the effect of fraxetin and PF-4708671 on migration and invasion of A375 cells. Results Fraxetin and PF-4708671 significantly inhibited the proliferation, migration and invasion of A375 cells (P < 0.05, 0.01). Fraxetin and PF-4708671 significantly inhibited the p70S6K/S6 pathway activity, down-regulated the expressions of mesenchymal proteins and matrix metalloproteinases (P < 0.05, 0.01). Conclusion Fraxetin may inhibit the proliferation, migration and invasion of A375 cells by down-regulating p70S6K.

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湖南省药学应用特色学科资金资助项目（湘教通[2018]469号）；国家级大学生创新创业训练计划项目（202010316013G）