CYTOTOXIC ANALOG OF SOMATOSTATIN CONTAINING METHOTREXATE INHIBITS GROWTH OF MIA PACA-2 HUMAN PANCREATIC-CANCER XENOGRAFTS IN NUDE-MICE

Citation
S. Radulovic et al., CYTOTOXIC ANALOG OF SOMATOSTATIN CONTAINING METHOTREXATE INHIBITS GROWTH OF MIA PACA-2 HUMAN PANCREATIC-CANCER XENOGRAFTS IN NUDE-MICE, Cancer letters, 62(3), 1992, pp. 263-271
Citations number
31
Language
INGLESE
art.tipo
Article
Journal title
ISSN journal
0304-3835
Volume
62
Issue
3
Year of publication
1992
Pages
263 - 271
Database
ISI
SICI code
0304-3835(1992)62:3<263:CAOSCM>2.0.ZU;2-T
Abstract
Nude mice bearing xenografts of MIA PaCa-2 human pancreatic cancer cel l line were treated for 4 weeks with AN-51, a somatostatin octapeptide analog D-Phe-C activated ys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) co ntaining methotrexate attached to the alpha-amino group of D-Phe in po sition 1. Control groups of mice received saline, RC-121 or methotrexa te. Drugs were given in equimolar doses by daily s.c. injections. Afte r 7 days of treatment with 25-mu-g/day of AN-51, tumor growth was comp letely inhibited although the treatment had to be suspended because of toxic side effects, especially on the gastrointestinal tract, accompa nied by major weight loss of the animals. Mice were allowed to recover for 1 week and treatment was continued with 12.5-mu-g/day AN-51. Afte r 2 weeks of additional therapy, tumor volume, percentage change in tu mor volume, and tumor weights were significantly decreased, compared w ith controls, only in the group treated with AN-51. Methotrexate and R C-121 also inhibited tumor growth, but their effects were not statisti cally significant. AN-51 retained its hormonal activity and decreased serum growth hormone levels in mice. Binding affinity of AN-51 for som atostatin receptors on MIA PaCa-2 cells was found to be 2.5-times lowe r than that of parent compound RC-121. This is the first report on inh ibition of human pancreatic cancer growth in vivo by somatostatin anal ogs carrying cytotoxic radicals.