Physalin A exerts anti-tumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling.
Physalin A exerts anti-tumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling.
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DOI：
10.18632/oncotarget.7051
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发表时间：
2016-02-23
期刊：
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
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作者：
Zhu F;Dai C;Fu Y;Loo JF;Xia D;Gao SP;Ma Z;Chen Z
信号转导和转录激活因子3(STAT3)信号通路在包括非小细胞肺癌(NSCLC)在内的多种人类癌症的发生和发展中起着关键作用。在这项研究中，我们旨在评价酸浆甲素的治疗潜力，这是一种从酸浆中提取的具有内酯活性的化合物。中药中使用的Fraceti在人非小细胞肺癌细胞中进行了评估。并确定其是否通过抑制JAK2和JAK3的磷酸化水平而抑制STAT3的固有活性和诱导活性，从而对NSCLC细胞产生抗增殖和促凋亡作用，以及。在小鼠NSCLC细胞体内移植模型中，验证了酸浆甲素的抗肿瘤作用。在含有STAT3的非小细胞肺癌细胞中，PHASALIN A具有抗增殖和促凋亡作用；它还通过调节JAK2和JAK3的磷酸化来抑制STAT3的结构性和诱导性活性。此外，酸浆甲素抑制了STAT3的核转位和转录活性，从而降低了STAT3及其靶基因如Bcl2和XIAP的表达水平。小干扰RNA(SiRNA)抑制STAT3的表达可显著增强PHASALIN A对NSCLC细胞的促凋亡作用。此外，酸浆甲素显著抑制肿瘤移植瘤的生长。因此，作为JAK2/3-STAT3信号通路的抑制剂，酸浆甲素具有很强的抗肿瘤活性，这可能有助于开发治疗非小细胞肺癌的治疗策略。
The signal transducers and activators of transcription 3 (STAT3) signaling pathway plays critical roles in the pathogenesis and progression of various human cancers, including non-small cell lung cancer (NSCLC). In this study, we aimed to evaluate the therapeutic potential of physalin A, a bioactive withanolide derived from Physalis alkekengi var. francheti used in traditional Chinese medicine, was evaluated in human NSCLC cells. Its and determined whether it effect oninhibited both constitutive and induced STAT3 activity, through repressing the phosphorylation levels of JAK2 and JAK3, resulting in anti-proliferation and pro-apoptotic effects on NSCLC cells was also determined, and. theThe antitumor effects of physalin A were also validated usingin an in vivo mouse xenograft models of NSCLC cells. Physalin A had anti-proliferative and pro-apoptotic effects in NSCLC cells with constitutively activated STAT3; it also suppressed both constitutive and induced STAT3 activity by modulating the phosphorylation of JAK2 and JAK3. Furthermore, physalin A abrogated the nuclear translocation and transcriptional activity of STAT3, thereby decreasing the expression levels of STAT3, its target genes, such as Bcl-2 and XIAP. Knockdown of STAT3 expression by small interfering RNA (siRNA) significantly enhanced the pro-apoptotic effects of physalin A in NSCLC cells. Moreover, physalin A significantly suppressed tumor xenograft growth. Thus, as an inhibitor of JAK2/3-STAT3 signaling, physalin A, has potent anti-tumor activities, which may facilitate the development of a therapeutic strategy for treating NSCLC.