Cellular pharmacology of P-ethoxy antisense oligonucleotides targeted to Bcl-2 in a follicular lymphoma cell line.
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 microM, 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.
Gutiérrez-Puente
Yolanda
Y
Immunobiology and Drug Carriers Section, Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Tari
Ana M
AM
Ford
Richard J
RJ
Tamez-Guerra
Reyes
R
Mercado-Hernandez
Roberto
R
Santoyo-Stephano
Martha
M
Lopez-Berestein
Gabriel
G
D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D016503:Drug Delivery Systems; D005019:Ethyl Ethers / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018390:Gene Targeting; D006801:Humans; D008081:Liposomes; D008224:Lymphoma, Follicular / Q000235:genetics / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D005019:Ethyl Ethers; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger