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

Abstract Since multicellular resistance (MCR) has been shown to be as adhesion-dependent, the role of αv integrin in MCR of HT29 was investigated in this paper. Down-regulation of αv integrin reduced MCR to oxaliplatin, but did not detectably change the drug sensitivity of monolayers. Down-regulation of αv integrin decreased phosphorylated NF-κB 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 αv integrin, cell–cell contact may contribute to activation of αv integrin, through which increasing phosphorylated p65 and decreasing phosphorylated JNK2 takes part in MCR.