Down-regulation of αv integrin by retroviral delivery of small interfering RNA reduces multicellular resistance of HT29

Down-regulation of αv integrin by retroviral delivery of small interfering RNA reduces multicellular resistance of HT29
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DOI:
10.1016/j.canlet.2009.04.023
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发表时间:
2009-11-01
期刊:
影响因子:
9.7
通讯作者:
Liang, Hou-jie
Liang, Hou-jie
中科院分区:
医学1区
文献类型:
--
作者:
He, Jian-ming;Wang, Feng-chao;Liang, Hou-jie

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由于多细胞耐药(MCR)已被证明是粘附依赖性的,因此本文研究了α v整合素在HT29的MCR中的作用。α v整合素的下调降低了MCR对奥沙利铂的反应,但没有明显改变单层膜的药物敏感性。α v整合素的下调降低了多细胞球体中磷酸化的NF-kappa B p65,并增加了磷酸化的JNK2。多细胞球体的细胞-细胞粘附和细胞-细胞连接与体内情况相似。由于包括粘附在内的力可以激活α v整合素,细胞-细胞接触可能有助于α v整合素的激活,通过磷酸化p65的增加和磷酸化JNK2的减少参与MCR。2009爱思唯尔爱尔兰有限公司版权所有。
Since multicellular resistance (MCR) has been shown to be as adhesion-dependent, the role of alpha v integrin in MCR of HT29 was investigated in this paper. Down-regulation of alpha v integrin reduced MCR to oxaliplatin, but did not detectably change the drug sensitivity of monolayers. Down-regulation of alpha v integrin decreased phosphorylated NF-kappa B p65 and increased phosphorylated JNK2 in multicellular spheroids. Cell-cell adhesion and cell-cell junctions in multicellular spheroids resembled the in vivo situation. Since force, including adhesion, can activate alpha v integrin, cell-cell contact may contribute to activation of alpha v integrin, through which increasing phosphorylated p65 and decreasing phosphorylated JNK2 takes part in MCR. (C) 2009 Elsevier Ireland Ltd. All rights reserved.