Verteporfin inhibits growth of human glioma in vitro without light activation.
Verteporfin inhibits growth of human glioma in vitro without light activation.
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DOI：
10.1038/s41598-017-07632-8
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发表时间：
2017-08-08
影响因子：
4.6
通讯作者：
Vavvas DG
中科院分区：
文献类型：
--
作者：
Al-Moujahed A;Brodowska K;Stryjewski TP;Efstathiou NE;Vasilikos I;Cichy J;Miller JW;Gragoudas E;Vavvas DG
维替泊芬（VP）是一种用于光动力疗法的光激活药物，用于治疗脉络膜新生血管膜，也被证明是恶性细胞的有效抑制剂。最近的研究表明，即使没有光激活，VP仍可能通过抑制YAP-TEAD复合物来抑制某些肿瘤细胞系，包括卵巢癌、肝癌和视网膜母细胞瘤。在这项研究中，我们检查了没有光激活的 VP 对人神经胶质瘤细胞系（LN229 和 SNB19）的影响。通过蛋白质印迹分析，我们发现，在没有光激活的情况下暴露于 VP 的人胶质瘤细胞表现出 YAP-TEAD 相关下游信号分子的下调，包括 c-myc、axl、CTGF、cyr61 和 survivin，以及肿瘤生长抑制剂分子 p38 MAPK 的上调。此外，我们观察到 VEGFA 和多能标记物 Oct-4 的表达也下降。维替泊芬不会改变 Akt 生存途径或 mTor 途径，但 LC3-IIB（自噬体生物发生的标志物）略有增加。这项研究表明，应进一步探索维替泊芬作为胶质母细胞瘤治疗的辅助疗法。
Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19). Through western blot analysis, we identified that human glioma cells that were exposed to VP without light activation demonstrated a downregulation of YAP-TEAD-associated downstream signaling molecules, including c-myc, axl, CTGF, cyr61 and survivin and upregulation of the tumor growth inhibitor molecule p38 MAPK. In addition, we observed that expression of VEGFA and the pluripotent marker Oct-4 were also decreased. Verteporfin did not alter the Akt survival pathway or the mTor pathway but there was a modest increase in LC3-IIB, a marker of autophagosome biogenesis. This study suggests that verteporfin should be further explored as an adjuvant therapy for the treatment of glioblastoma.