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

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.