Sci Rep:醉茄素A抑制非小细胞肺癌上皮细胞向间充质细胞的转化

2018-10-27 xiangting MedSci原创

这项研究提供了额外的证据,表明WFA对NSCLC细胞EMT诱导的抑制作用,并进一步证明了WFA对NSCLC转移的治疗潜力。

肺癌是全世界和美国癌症相关死亡的首要原因。尽管最近治疗方法有所进展,转移仍是肺癌治疗中的主要挑战,并导致了极差的预后。上皮细胞向间充质细胞转化(EMT),由于其在非小细胞肺癌NSCLC)转移中起重要作用,这一细胞重编程的复杂过程已成为一个具有吸引力的药物治疗靶点。这项研究检测了醉茄素A(WFA),一种植物来源的甾体内酯在人类NSCLC细胞系中对EMT的影响。

首先,研究证明了WFA对A549和H1299 NSCLC细胞具有时间和浓度依赖性细胞毒性。然后,将细胞暴露于≤0.5μMWFA中≤4小时,以最小化细胞毒性并确定其对EMT、细胞粘附、运动性、迁移和侵袭的影响。通过在含TGFβ1(5ng/mL)和TNFα(25ng/mL)的无血清培养基中培养细胞48小时进行EMT诱导。观察到使用WFA预处理的细胞抑制细胞粘附、迁移和A549、H1299细胞的侵袭。使用免疫印迹、免疫荧光和qRT-PCR分析,研究人员证明WFA在两种细胞系中抑制TGFβ1和TNFα诱导的EMT。机制上来讲,WFA抑制A549和H1299细胞中的磷酸化和Smad2/3和NF-κB的核转位。

总之,这项研究提供了额外的证据,表明WFA对NSCLC细胞EMT诱导的抑制作用,并进一步证明了WFA对NSCLC转移的治疗潜力。

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    2018-10-27 kafei

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