Inhibition of proliferation by L-myc antisense DNA for the translational initiation site in human small cell lung cancer.
We evaluated the antiproliferative effect of L-myc antisense DNA in NCI-H209, a human small cell lung cancer (SCLC) cell line overexpressing the L-myc gene. The synthetic DNA used in the present study was oligodeoxynucleoside phosphorothioate, which showed rapid incorporation into NCI-H209 cells and localized mainly in the cell nucleus and weakly in the cytoplasm. The exposure of this cell line to L-myc antisense DNA covering the translational initiation site of L-myc proteins inhibited the cell proliferation in a dose-dependent sequence-specific manner. Furthermore, the growth inhibition by this antisense DNA was correlated with the level of L-myc expression in three SCLC cell lines, NCI-H209, NCI-H510, and NCI-H82. In Western blot analysis, expression of the L-myc proteins was down-regulated in the antisense-treated cells compared with control-treated cells in NCI-H209. Together with unique characteristics of the L-myc gene, including: (a) a frequently amplified and overexpressed state in SCLC; and (b) very restricted and low-level expression in human adult tissues, the present data indicate that L-myc is a good candidate for the target gene for antisense DNA therapy based on molecular biological diagnosis in SCLC.
Dosaka-Akita
H
H
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Akie
K
K
Hiroumi
H
H
Kinoshita
I
I
Kawakami
Y
Y
Murakami
A
A
D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D016373:DNA, Antisense / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016259:Genes, myc; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013872:Thionucleosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D016271:Proto-Oncogene Proteins c-myc; D013872:Thionucleosides