Down-regulation of alphav 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 alphav integrin in MCR of HT29 was investigated in this paper. Down-regulation of alphav integrin reduced MCR to oxaliplatin, but did not detectably change the drug sensitivity of monolayers. Down-regulation of alphav integrin decreased phosphorylated NF-kappaB 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 alphav integrin, cell-cell contact may contribute to activation of alphav integrin, through which increasing phosphorylated p65 and decreasing phosphorylated JNK2 takes part in MCR.