Radiation Oncology and Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Ultrasound Med Biol. 2012 Nov;38(11):1958-69. doi: 10.1016/j.ultrasmedbio.2012.07.009. Epub 2012 Sep 12.
Ultrasound can be used to target endothelial cells in cancer therapy where the destruction of vasculature leads to tumor cell death. Here, we demonstrate ultrasound bioeffects in which the levels of genes in endothelial cells can be significantly altered by ultrasound-stimulated microbubble exposure. These were compared with established effects of radiation on endothelial cells at a gene level. Human-endothelial cells were exposed to ultrasound and microbubbles, radiation or combinations of ultrasound, microbubbles and radiation. Gene expression analyses revealed an up-regulation of genes known to be involved in apoptosis and ceramide-induced apoptotic pathways, including SMPD2, UGT8, COX6B1, Caspase 9 and MAP2K1 with ultrasound-stimulated microbubble exposure but not SMPD1. This was supported by immunohistochemistry and morphologic changes examined with cell microscopy, which showed changes in SMPD1 gene product in cells with microbubble exposure. This supports the hypothesis that ultrasound-stimulated microbubbles can induce significant bioeffect-related changes in gene expression and can affect ceramide signaling pathways in endothelial cells, leading to apoptosis.
超声可用于癌症治疗中的靶向内皮细胞，血管破坏可导致肿瘤细胞死亡。在这里，我们展示了超声生物效应，其中超声刺激微泡暴露可显著改变内皮细胞中的基因水平。将这些与辐射对内皮细胞在基因水平上的既定影响进行了比较。将人内皮细胞暴露于超声和微泡、辐射或超声、微泡和辐射的组合中。基因表达分析显示，与凋亡和神经酰胺诱导的凋亡途径相关的基因的上调，包括 SMPD2、UGT8、COX6B1、Caspase 9 和 MAP2K1，与超声刺激的微泡暴露有关，但与 SMPD1 无关。这得到了免疫组织化学和细胞显微镜检查的形态变化的支持，显示了微泡暴露细胞中 SMPD1 基因产物的变化。这支持了这样一种假设，即超声刺激的微泡可以诱导基因表达的显著生物效应相关变化，并影响内皮细胞中的神经酰胺信号通路，导致细胞凋亡。
