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The Synthetic Hepatic Peptides Pyroglutamylglutamylglycylserylasparagine and Pyroglutamylglutamylglycylserylaspartic Acid Inhibit Growth of MH₁C₁ Rat Hepatoma Cells Transplanted into Buffalo Rats or Athymic Mice¹

Institute of Pathology [J. E. P., K. E.], Department of Clinical Pharmacology [K. S. H., H. E. R.], and Pediatric Research Institute [K. L. R.], Rikshospitalet, N-0027 Oslo 1, Norway

Repeated i.p. injections of the synthetic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibited the long-term growth of MH₁C₁ rat hepatoma cells by 50–70% in three in vivo models: metastatic colony growth in the lungs of young Buffalo rats; s.c. tumor growth in young Buffalo rats; and s.c. tumor growth in athymic mice. The amide free peptide pyroglutamylglutamylglycylserylaspartic acid which inhibited the tumor growth in all the models showed a curvilinear dose-response relationship with a maximal effect at 1000 pmol/animal in mice and at 100 pmol/animal in rats. The amidated peptide pyroglutamylglutamylglycylserylasparagine, which was only tested in the lung model, showed growth inhibition with 2, 20, or 200 pmol/animal, but 200 pmol/animal was most effective. We have recently reported that these peptides show cochromatography with hepatic growth inhibitory peptides, isolated from mouse liver.

¹ This work was supported by The Norwegian Cancer Society and Hafslund Nycomed Bioreg AS, Oslo, Norway.

Received 6/ 7/91. Accepted 12/13/91.