Detecting human melanoma cell re-differentiation following BRAF or heat shock protein 90 inhibition using photoacoustic and magnetic resonance imaging.
Detecting human melanoma cell re-differentiation following BRAF or heat shock protein 90 inhibition using photoacoustic and magnetic resonance imaging.
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DOI：
10.1038/s41598-017-07864-8
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发表时间：
2017-08-15
影响因子：
4.6
通讯作者：
Beloueche-Babari M
中科院分区：
文献类型：
--
作者：
Shah A;Delgado-Goni T;Casals Galobart T;Wantuch S;Jamin Y;Leach MO;Robinson SP;Bamber J;Beloueche-Babari M
近年来，针对BRAF-MEK-ERK信号通路的靶向治疗在恶性黑色素瘤的治疗中显示出了巨大的前景，这些药物现已广泛应用于临床。已知使用这些试剂处理的黑素瘤细胞表现出增加的黑色素和酪氨酸酶活性水平。在这项研究中，我们评估了非侵入性成像方法（光声成像（派）和磁共振成像（MRI））检测SKMEL 28人黑色素瘤细胞中黑色素诱导的潜力，分别使用17-AAG和vemurafenib抑制Hsp 90和BRAF信号传导。我们使用蛋白质印迹和分光光度法证实，与对照细胞相比，Hsp 90或BRAF受体诱导的黑色素瘤细胞分化导致酪氨酸酶和黑色素表达水平上调。这种治疗后细胞色素沉着的增加诱导了派信号的显着增加，这是光谱识别和MRI弛豫时间T1和缩短。这项概念验证研究证明了MRI和派检测黑色素瘤细胞中Hsp 90和BRAF-MEK靶向治疗诱导的下游细胞变化的潜力，对体内成像具有潜在意义。
Targeted therapies specific to the BRAF-MEK-ERK signaling pathway have shown great promise in the treatment of malignant melanoma in the last few years, with these drugs now commonly used in clinic. Melanoma cells treated using these agents are known to exhibit increased levels of melanin pigment and tyrosinase activity. In this study we assessed the potential of non-invasive imaging approaches (photoacoustic imaging (PAI) and magnetic resonance imaging (MRI)) to detect melanin induction in SKMEL28 human melanoma cells, following inhibition of Hsp90 and BRAF signaling using 17-AAG and vemurafenib, respectively. We confirmed, using western blot and spectrophotometry, that Hsp90 or BRAF inhibitor-induced melanoma cell differentiation resulted in an upregulation of tyrosinase and melanin expression levels, in comparison to control cells. This post-treatment increase in cellular pigmentation induced a significant increase in PAI signals that are spectrally identifiable and shortening of the MRI relaxation times T 1 and . This proof-of-concept study demonstrates the potential of MRI and PAI for detecting the downstream cellular changes induced by Hsp90 and BRAF-MEK-targeted therapies in melanoma cells with potential significance for in vivo imaging.
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