Reversible inhibition of IL-8 receptor B mRNA expression and proliferation in non-small cell lung cancer by antisense oligonucleotides.
We examined the importance of IL-8 receptor B mRNA expression in the growth of non-small cell lung cancer (NSCLC). Using antisense oligonucleotide ICN 197, we were able to inhibit IL-8 R B mRNA expression in vitro. The sequence specific effect of antisense oligonucleotide and down-regulation of IL-8 R B mRNA was shown by Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Southern blot analysis. The proliferation of treated cells was measured by 3H thymidine incorporation. We found that treatment of NSCLC cells caused reversible growth inhibition and reversible down regulation of IL-8 R B mRNA. Furthermore, we observed that the treatment of nude mice with oligonucleotide ICN 197 inhibited the growth of tumors developed from NSCLC cells injected subcutaneously. Our data in vitro suggest that IL-8 receptor B mRNA expression is required to maintain the proliferative rate of NSCLC. Based on the data in vivo. oligonucleotide ICN 197 may be considered for the development of novel therapeutic treatment for lung cancer.
Olbina
G
G
Research Department, ICN Pharmaceuticals, Inc., Costa Mesa, CA 92626, USA.
Cieslak
D
D
Ruzdijic
S
S
Esler
C
C
An
Z
Z
Wang
X
X
Hoffman
R
R
Seifert
W
W
Pietrzkowski
Z
Z
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000378:metabolism; D023062:Receptors, Interleukin-8A; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A