Induction of Apoptosis in Small-Cell Lung Cancer Cells by an Antisense Oligodeoxynucleotide Targeting the Bcl-2 Coding Sequence

Abstract

We have identified a novel antisense ODN sequence (ODN 2009) that effectively reduces the viability of small-cell lung cancer cells by reducing Bcl-2 levels and facilitating apoptosis.

Synergistic cytotoxicity of bcl-2 antisense oligodeoxynucleotides and etoposide, doxorubicin and cisplatin on small-cell lung cancer cell lines

“…Once the optimal growth conditions have been established for each cell line. the WST-1 viabilitv assav provides reproducible results which correlate well with the actual number of X iable cells determined by propidium iodide exclusion (Ziegler et al 1997 Germanv) was added per well and allowed to react for 3-5 h at 37"C. Absorbance at 450 nm was measured by use of an enzx-melinked immunosorbent assav reader (2550 EIA reader. Bio Rad Laboratories.…”

“…Recently. we has-e identified an antisense sequence (ODN 2009) targeting the bcl-2 coding region that effectixelv downregulated bcl-2 expression and induced apoptosis in SCLC cells (Ziegler et al 1997). In the present study.…”

“…The cytotoxic effects of ODN 2009 and chemotherapeutic agents on SCLC cell lines were determined by use of the colorimetric WST-1Iiabilitx assav as described previously (Ziegler et al 1997). Once the optimal growth conditions have been established for each cell line.…”

“…Only' cells that excluded propidium iodide w ere considered Xiable. Apoptotic cell death after cvtotoxic treatment was confirmed by forward and side light scatter analy-sis as described prexviouslV (Cotter et al 1992: Ziegler et al 1997). …”

Transfer of bcl-xs plasmid is effective in preventing and inhibiting rat hepatocellular carcinoma induced by N-nitrosomorpholine

“…1,2 Because anti-apoptotic proteins, bcl-2 and bcl-xL, are often enhanced in various cancers, where they may play a pivotal role in tumor initiation and progression, 3,4 bcl-2 and bcl-xL genes were suggested to be targets for cancer gene therapy. Administrations of bcl-2 and bcl-xL antisense oligonucleotides promoted apoptosis and inhibited cell growth in brest carcinoma cells 5 and small-cell lung cancer cells, 6 in which bcl-2 or bcl-xL was detectable. In our previous report, 7 we examined the effects of in vivo electroporetic transfer of a bcl-2 antisense oluigonucleotide phosphorothioate on rat hepatocarcinogenesis, and showed that bcl-2 antisense oligonucleotide inhibited expression of bcl-2 mRNA and the occurrence and growth of rat hepatocellular carcinoma induced by NNM.…”