Nude mice bearing xenografts of MIA PaCa-2 human
pancreatic cancer cell line were treated for 4 weeks with AN-51, a
somatostatin octapeptide analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) containing
methotrexate attached to the alpha-amino group of D-Phe in position 1. Control groups of mice received saline,
RC-121 or
methotrexate. Drugs were given in equimolar doses by daily s.c.
injections. After 7 days of treatment with 25 micrograms/day of AN-51,
tumor growth was completely inhibited although the treatment had to be suspended because of toxic side effects, especially on the gastrointestinal tract, accompanied by major
weight loss of the animals. Mice were allowed to recover for 1 week and treatment was continued with 12.5 micrograms/day AN-51. After 2 weeks of additional
therapy,
tumor volume, percentage change in
tumor volume, and
tumor weights were significantly decreased, compared with controls, only in the group treated with AN-51.
Methotrexate and
RC-121 also inhibited
tumor growth, but their effects were not statistically significant. AN-51 retained its hormonal activity and decreased serum
growth hormone levels in mice. Binding affinity of AN-51 for
somatostatin receptors on MIA PaCa-2 cells was found to be 2.5-times lower than that of parent compound
RC-121. This is the first report on inhibition of human
pancreatic cancer growth in vivo by
somatostatin analogs carrying cytotoxic radicals.