Increased sensitivity to cisplatin in gastric cancer by antisense inhibition of the HER-2/neu (c-erbB-2) gene

Tadao Funato, Kanoko Kozawa, Shinichi Fujimaki, Toshihiko Miura, Mitsuo Kaku

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Background: The c-erbB-2 oncogene encodes a transmembrane tyrosine kinase receptor and its abnormal expression may be related to the prognosis of gastric cancer. Gastric cancer is relatively resistant to various drugs, including cisplatin. Cisplatin is widely used in cancer chemotherapy, but the mechanisms of drug resistance are not yet known. Methods: We used the human gastric cancer cell lines MKN-7 and KATO-III, which express the c-erbB-2 oncogene, as a model for relative resistance to cisplatin. We investigated whether inhibition with anti-sense oligonucleotides against c-erbB-2 increased the sensitivity of MKN-7 and KATO-III cells to cisplatin. Results: Antisense oligonucleotides for c-erbB-2 inhibited the expression of c-erbB-2 mRNA and protein and increased sensitivity to cisplatin, but not to other drugs, in MKN-7 and KATO-III cells. Cell growth was also inhibited by c-erbB-2 anti-sense oligonucleotides but not sense oligonucleotides. Conclusions: These findings indicate that c-erbB-2 expression in gastric cancer is one of the factors related to cisplatin sensitivity, and that anti-c-erbB-2 antisense oligonucleotides induced increased sensitivity to cisplatin.

Original languageEnglish
Pages (from-to)297-303
Number of pages7
JournalChemotherapy
Volume47
Issue number4
DOIs
Publication statusPublished - 2001 Jul 9

Keywords

  • Antisense oligonucleotides
  • Cisplatin
  • Flow cytometry
  • Gastric cancer
  • c-erbB-2

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)
  • Infectious Diseases

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