Growth inhibition and antimetastatic effect of antisense poly-DNP-RNA on human breast cancer cells.
The RNase-resistant and membrane-permeable antisense poly-2'-O-(2,4-dinitrophenyl)-oligoribonucleotides (poly-DNP-RNA) against RIalpha subunit of protein kinase A (RIalpha/PKA) has been used to inhibit the growth of human breast cancer MDA-MB-231 cells in vitro and in vivo. This antisense poly-DNP-RNA, with oligonucleotide sequence GGGCGUGCCUCCUCACUGGC, was found to be an effective concentration-dependent inhibitor of MDA-MB-231 cell line, whereas the control poly-DNP-RNAs with either random or sense sequence were found completely inactive. In situ hybridization studies showed that this antisense inhibitor can permeate spontaneously into MDA-MB-231 cells and distribute itself throughout the cytoplasm. Intraperitoneal administration of this antisense RIalpha poly-DNP-RNA to SCID mice with transplanted MDA-MB-231 cells was found to inhibit the growth of the xenografts in a concentration-dependent way, prevent metastasis, and drastically reduce mortality.
Ru
K
K
Bioenergetics Laboratory, Natural Sciences Complex, State University of New York, Buffalo 14260-3000, USA. kunru@acsu.buffalo.edu
Schmitt
S
S
James
W I
WI
Wang
J H
JH
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020320:Oligoribonucleotides, Antisense