Contiguous Four‐guanosine Sequence in c‐myc Antisense Phosphorothioate Oligonucleotides Inhibits Cell Growth on Human Lung Cancer Cells: Possible Involvement of Cell Adhesion Inhibition

A contiguous four‐guanosine (4G) sequence in c‐myc antisense phosphorothioate oligonucleotides caused an antiproliferative effect in smooth muscle cells. To investigate the antiproliferative effect of c‐myc antisense oligonucleotides on human lung cancer cell lines, we synthesized oligonucleotides of various lengths and sequences, focusing on the contiguous four‐guanosine (4G) sequence. While a c‐myc antisense oligonucleotide (20AS1 (4G)) targeted to the translation initiation codon of c‐myc mRNA inhibited cell growth of A549 cells by 69% at 10 μM, a scrambled oligonucleotide (20SCR1 (4G)) containing the contiguous four‐guanosine (4G) sequence also inhibited cell growth by 72% at the same dose. Although treatment with either 20AS1 (4G) or 20SCR1 (4G) inhibited cell adhesion by 70% at 10 μM, expression of c‐myc protein was significantly suppressed only by 20AS1 (4G) (62%), and was only weakly inhibited by 20SCR1 (4G) (32%). Furthermore, a small cell lung carcinoma cell line, Lu65, which can grow in suspension form, was highly resistant to 20AS1 (4G) treatment (IC(50)>20 μM). These results suggest that the cell growth inhibition by C‐myc antisense oligonucleotides containing the contiguous four‐guanosine (4G) sequence was possibly correlated with inhibition of cell adhesion, but not with inhibition of c‐myc protein expression, via a sequence‐specific non‐antisense mechanism.