c-met Antisense Oligonucleotides Inhibit Proliferation or Invasiveness of Gastric Cancer Cells

Masahide Kaji, Yonemura Yutaka, Yasuo Hirono, Kouichirou Tsugawa, Sachio Fushida, Takashi Fujimura, Kouichi Miwa, Itsuo Miyazaki

Second Department of Surgery, Kanazawa University School of Medicine

We first screened for c-met expression in human gastric cancer cell lines, MKN-28, MKN-45 and TMK-1, by Northern blot analysis. The rank order of c-met mRNA abundance in these cell lines was MKN-45>TMK-1>MKN-28. Next, to test whether the growth and invasion of gastric cancer cells depend on c-met, we prepared phosphorothioate-type antisense oligonucleotides that were complementary to human c-met mRNA. We conducted experiments to determine whether blocking expression of the c-met gene with the antisense molecules affected either the proliferative or the invasive phenotype of the cancer cells. The growth of MKN-45 cells was markedly inhibited by the antisense c-met oligonucleotides, in a dose-dependent manner, but not by sense controls. The antisense oligonucleotides also effectively inhibited the migration of TMK-1 cells. These results indicate that c-met gene products may be causally related to the proliferation or invasion of gastric cancer cells, and that antisense c-met DNA has therapeutic potential in that it may facilitate circumventing the progression of gastric cancers.

Key words
c-met, antisense DNA, gastric cancer

Reprint requests
Masahide Kaji Second Department of Surgey, Kanazawa University School of Medicine
13-1 Takara-machi, Kanazawa, 920 JAPAN

Accepted
December 11, 1996

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