Cellular Pharmacology of P-ethoxy Antisense Oligonucleotides Targeted to Bcl-2 in a Follicular Lymphoma Cell Line

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Abstract
A P-ethoxy oligonucleotide (oligo), 20 bases long and specific for the translation initiation site of human Bcl-2 mRNA, was incorporated into liposomes to increase its intracellular delivery. This oligo selectively inhibited Bcl-2 protein expression and induced growth inhibition in t(14;18)-positive transformed follicular lymphoma (FL) cell lines. We studied the inhibitory effects of shorter liposomal P-ethoxy oligos (7, 9, 11 or 15 mer) in order to determine the activity of different oligo chain lengths targeted to the same Bcl-2 mRNA. At 12 μM, all the oligos inhibited the growth of a FL cell line. We compared the 7-mer oligo with the 20-mer oligo. The two oligos inhibited Bcl-2 protein expression similarly: 66% and 60% for the 7- and 20-mer, respectively. The uptake and retention of both oligos were also very similar. Our results indicate that the Bcl-2 inhibitory activity is maintained with P-ethoxy antisense oligos ranging from 7 to 20 bases.