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

被引:21
作者
He, Jian-ming [1 ]
Wang, Feng-chao [2 ]
Qi, Hua-bing [2 ]
Li, Yan [1 ]
Liang, Hou-jie [1 ]
机构
[1] Third Mil Med Univ, Southwest Hosp, Dept Oncol, Chongqing 400038, Peoples R China
[2] Third Mil Med Univ, State Key Lab Trauma Burns & Combined Injury, Chongqing 400038, Peoples R China
关键词
Integrin; Oxaliplatin; Chemotherapy; Multicellular resistance; Colon cancer; NF-KAPPA-B; GROWTH-FACTOR; CELL-SURVIVAL; SHEAR-STRESS; E-CADHERIN; ACTIVATION; INTEGRIN-ALPHA(V)BETA(3); EXPRESSION; ADHESION; MATRIX;
D O I
10.1016/j.canlet.2009.04.023
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:182 / 188
页数:7
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