Down-regulation of alphav 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 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.
He
Jian-Ming
JM
Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Wang
Feng-Chao
FC
Qi
Hua-Bing
HB
Li
Yan
Y
Liang
Hou-Jie
HJ
D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000637:transplantation; D003110:Colonic Neoplasms / Q000473:pathology* / Q000628:therapy; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000494:pharmacology* / Q000627:therapeutic use; D039564:Integrin alphaV / Q000096:biosynthesis / Q000235:genetics*; D048688:MAP Kinase Kinase 7 / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology*; D012190:Retroviridae / Q000235:genetics*; D018874:Spheroids, Cellular / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D018906:Antineoplastic Agents, Alkylating; D039564:Integrin alphaV; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; C498143:RELA protein, human; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D000077150:Oxaliplatin; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human