Inhibition of human carcinoma and neuroblastoma cell proliferation by anti-c-myc siRNA.
Suppression of c-myc proto-oncogene expression by small interfering RNA (siRNA) in human epidermoid carcinoma KB-3-1 and neuroblastoma SK-N-MC cell lines was investigated. The siRNA duplex targeted to the exon 3 of c-myc mRNA (siRNA-I) was prepared by in vitro transcription using T7 RNA polymerase and short double-stranded DNA (dsDNA) templates. siRNA-I was shown to efficiently decrease c-myc mRNA expression in both tumor cell lines and to arrest their proliferation. Incubation of KB-3-1 cells with 150 nM siRNA-I results in a 92% decrease in the c-myc mRNA level and an 83% decrease in the protein level. In SK-N-MC cells, 150 nM siRNA-I causes a 60% decrease in the c-myc mRNA level and a 55% decrease in the protein level. The reduction of the c-myc mRNA level correlates with the inhibition of cell proliferation; 150 nM siRNA-I causes a 2.5-fold reduction in the SK-N-MC proliferation rate and a 15-fold decrease in the proliferation rate and complete arrest of cell division in KB-3-1 cells. siRNA-I has little effect on proliferation of the IMR-32 cells that overexpress the N-myc but not the c-myc gene, demonstrating that siRNA-I antiproliferation activity is mediated by specific block of c-myc expression.
Kabilova
Tatyana O
TO
Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia, 630090. kabilova@niboch.nsc.ru
Chernolovskaya
Elena L
EL
Vladimirova
Albina V
AV
Vlassov
Valentin V
VV
D002277:Carcinoma / Q000737:chemistry / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D009447:Neuroblastoma / Q000737:chemistry / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection
D016898:Interferon-alpha; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering