Low-Intensity Sonoporation-Induced Intracellular Signalling of Pancreatic Cancer Cells, Fibroblasts and Endothelial Cells.
Low-Intensity Sonoporation-Induced Intracellular Signalling of Pancreatic Cancer Cells, Fibroblasts and Endothelial Cells.
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DOI：
10.3390/pharmaceutics12111058
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发表时间：
2020-11-06
期刊：
影响因子：
5.4
通讯作者：
McCormack E
中科院分区：
文献类型：
--
作者：
Haugse R;Langer A;Murvold ET;Costea DE;Gjertsen BT;Gilja OH;Kotopoulis S;Ruiz de Garibay G;McCormack E
超声（US）和微泡（MB）的使用，通常被称为声孔效应，具有很大的潜力，以提高化疗的疗效。然而，介导声孔效应的分子机制尚不清楚，最近的研究表明，由US + MB诱导的细胞应激可能有助于治疗益处。此外，越来越多的人认识到，US + MB的作用不仅仅是癌细胞，还涉及肿瘤血管系统和微环境。我们将胰腺癌细胞（MIA PaCa-2）和基质细胞、成纤维细胞（BJ）和人脐静脉内皮细胞（HUVECs），用US ± MB，并研究细胞不可渗透染料的摄取程度。（钙黄绿素，通过流式细胞术），活力（细胞计数，膜联蛋白/PI和WST-1测定）以及在声致孔后立即和2小时（磷酸流式细胞术）在重要的细胞内信号传导途径中激活许多关键蛋白。不同细胞类型在所有这些方面对US ± MB的反应不同。通常，声致穿孔诱导MAP激酶（p38，ERK 1/2）的立即、瞬时活化，以及核糖体蛋白S6的磷酸化增加和4 E-BP 1的去磷酸化。声穿孔应激反应类似于在膜修复和恢复细胞稳态中对电穿孔和成孔毒素的细胞反应，并且可以在治疗上加以利用。基质细胞比肿瘤细胞对声孔作用更敏感，进一步优化声孔增强治疗的努力应针对微环境。
The use of ultrasound (US) and microbubbles (MB), usually referred to as sonoporation, has great potential to increase the efficacy of chemotherapy. However, the molecular mechanisms that mediate sonoporation response are not well-known, and recent research suggests that cell stress induced by US + MBs may contribute to the treatment benefit. Furthermore, there is a growing understanding that the effects of US + MBs are beyond only the cancer cells and involves the tumour vasculature and microenvironment. We treated pancreatic cancer cells (MIA PaCa-2) and stromal cells, fibroblasts (BJ) and human umbilical vein endothelial cells (HUVECs), with US ± MB, and investigated the extent of uptake of cell impermeable dye (calcein, by flow cytometry), viability (cell count, Annexin/PI and WST-1 assays) and activation of a number of key proteins in important intracellular signalling pathways immediately and 2 h after sonoporation (phospho flow cytometry). Different cell types responded differently to US ± MBs in all these aspects. In general, sonoporation induces immediate, transient activation of MAP-kinases (p38, ERK1/2), and an increase in phosphorylation of ribosomal protein S6 together with dephosphorylation of 4E-BP1. The sonoporation stress-response resembles cellular responses to electroporation and pore-forming toxins in membrane repair and restoring cellular homeostasis, and may be exploited therapeutically. The stromal cells were more sensitive to sonoporation than tumoural cells, and further efforts in optimising sonoporation-enhanced therapy should be targeted at the microenvironment.
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影响因子：
3.7
作者：
Hirabayashi F;Iwanaga K;Okinaga T;Takahashi O;Ariyoshi W;Suzuki R;Sugii M;Maruyama K;Tominaga K;Nishihara T
通讯作者：
Nishihara T
细胞周期特异性细胞对声孔反应的反应
影响因子：
12.4
作者：
Fan P;Zhang Y;Guo X;Cai C;Wang M;Yang D;Li Y;Tu J;Crum LA;Wu J;Zhang D
通讯作者：
Zhang D
影响因子：
2.9
作者：
Chen, Xian;Wan, Jennifer M. F.;Yu, Alfred C. H.
通讯作者：
Yu, Alfred C. H.
影响因子：
2.4
作者：
Guzmán, HR;Nguyen, DX;Prausnitz, MR
通讯作者：
Prausnitz, MR
影响因子：
4.9
作者：
Escoffre, J. M.;Piron, J.;Bouakaz, A.
通讯作者：
Bouakaz, A.