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.
Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Jian-Ming
JM
He
Feng-Chao
FC
Wang
Hua-Bing
HB
Qi
Yan
Y
Li
Hou-Jie
HJ
Liang
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