Phosphorothioated antisense c-myc oligonucleotide inhibits the growth of human colon carcinoma cells.
BACKGROUND
The functional significance of c-myc overexpression in human colon carcinoma is unclear.


METHODS
Three human colon carcinoma cell lines, LS174T, SW1116 and SW48, were treated in vitro with phosphorothioate modified antisense oligonucleotides (ASO), complementary to the c-myc translation initiation site, or two control oligonucleotides. Growth was assayed by the methyl tetrazolium (MTT) assay and colony formation. C-myc, retinoblastoma (Rb), carcinoembryonic antigen (CEA), and alkaline phosphatase (AP) expression was assessed by immunoblotting.


RESULTS
The ASO specifically inhibited growth of all three human colon carcinoma cell lines. Further studies were conducted on LS174T because growth inhibition was associated with a more differentiated morphology. In LS174T cells, ASO caused a dose dependent decrease in c-myc and Rb protein expression, but an increase in CEA and AP expression.


CONCLUSIONS
The growth of human colon carcinoma cells is dependent on c-myc expression, and the inhibition of c-myc expression in LS174T is associated with a more differentiated phenotype.
Yu
B W
BW
NCI-NMOB, National Naval Medical Center, Bethesda, MD 20889, USA.
Nguyen
D
D
Anderson
S
S
Allegra
C A
CA
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D001483:Base Sequence; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000633:toxicity*; D014176:Protein Biosynthesis / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D013873:Thionucleotides; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D002272:Carcinoembryonic Antigen; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D013873:Thionucleotides; D000469:Alkaline Phosphatase