Increased sensitivity to cisplatin in gastric cancer by antisense inhibition of the her-2/neu (c-erbB-2) gene.
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 antisense 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 antisense 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.
Funato
T
T
Division of Molecular Diagnostics, Department of Clinical Medicine, Tohoku University School of Medicine, Sendai, Japan. tfunato@mail.cc.tohoku.ac.jp
Kozawa
K
K
Fujimaki
S
S
Miura
T
T
Kaku
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D018734:Genes, erbB-2 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D018739:Oncogene Proteins v-erbB / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D018739:Oncogene Proteins v-erbB; D002945:Cisplatin