Modulation of apoptosis by endogenous Bcl-xL expression in MKN-45 human gastric cancer cells.

Abstract

This study was designed to clarify the role of endogenous Bcl-xL expression in modulating apoptosis of malignant cells. Administration of bcl-x-antisense oligonucleotides decreased Bcl-xL protein levels in the MKN-45 human gastric cancer cell line. The decrease in Bcl-xL protein content resulted in increased cell death induced by serum deprivation or Fas-antibody administration. Flow cytometric analysis revealed that the increased apoptotic cell death was more prominent in bcl-x-antisense-treated cells as compared to control cells, bcl-x-sense-treated cells, or bcl-x-nonsense-treated cells. To inhibit the effect of intrinsic Bcl-xL protein, we overexpressed Bak, which binds Bcl-xL and inhibits the anti-apoptotic effect of Bcl-xL, by transfection into MKN-45 cells. Bak-overexpressing cells showed increased apoptotic cell death induced by Fas-antibody when compared to parent cells and MKN-neo-transfected cells. Bak-overexpressing cells also showed greater sensitization to 5-fluorouracil and cisplatin than parent cells and MKN-neo-transfected cells. In conclusion, we demonstrated that administration of bcl-x-antisense oligonucleotides or overexpression of Bak protein induces sensitization to apoptosis in MKN-45 gastric cancer cells, suggesting that endogenous Bcl-xL expression in cancer cells is an important modulator of apoptosis.

• Authors: S Kondo, Y Shinomura, S Kanayama, Y Higashimoto, T Kiyohara, S Zushi, S Kitamura, H Ueyama, Y Matsuzawa
• Journal: Oncogene (Oncogene) Vol. 17 Issue 20 Pg. 2585-91 (Nov 19 1998) ISSN: 0950-9232 [Print] England
• PMID: 9840921 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• BAK1 protein, human
• BCL2L1 protein, human
• Culture Media, Serum-Free
• Membrane Proteins
• Neoplasm Proteins
• Oligonucleotides, Antisense
• Proto-Oncogene Proteins c-bcl-2
• Recombinant Fusion Proteins
• bcl-2 Homologous Antagonist-Killer Protein
• bcl-X Protein
• fas Receptor
• Cisplatin
• Fluorouracil

Topics

• Antibodies, Monoclonal (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (genetics)
• Cisplatin (pharmacology)
• Culture Media, Serum-Free
• Fluorouracil (pharmacology)
• Gene Expression Regulation, Neoplastic
• Humans
• Membrane Proteins (genetics, physiology)
• Neoplasm Proteins (physiology)
• Oligonucleotides, Antisense (pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, physiology)
• Recombinant Fusion Proteins (physiology)
• Stomach Neoplasms (genetics, metabolism, pathology)
• Tumor Cells, Cultured (drug effects)
• bcl-2 Homologous Antagonist-Killer Protein
• bcl-X Protein
• fas Receptor (immunology, physiology)