Abstract
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-C{A figure is presented}{A figure is presented}s-Thr-NH2(RC-121) containing methotrexate attached to the α-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 μg/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 μg/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.
| Original language | English |
|---|---|
| Pages (from-to) | 263-271 |
| Number of pages | 9 |
| Journal | Cancer Letters |
| Volume | 62 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 15 1992 |
| Externally published | Yes |
Fingerprint
Keywords
- methotrexate
- pancreatic cancer
- somatostatin
- somatostatin analog carrying cytotoxic radical
ASJC Scopus subject areas
- Cancer Research
- Molecular Biology
- Oncology
Cite this
Cytotoxic analog of somatostatin containing methotrexate inhibits growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice. / Radulovic, S.; Nagy, A.; Szoke, B.; Schally, Andrew V.
In: Cancer Letters, Vol. 62, No. 3, 15.03.1992, p. 263-271.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytotoxic analog of somatostatin containing methotrexate inhibits growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice
AU - Radulovic, S.
AU - Nagy, A.
AU - Szoke, B.
AU - Schally, Andrew V
PY - 1992/3/15
Y1 - 1992/3/15
N2 - 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-C{A figure is presented}{A figure is presented}s-Thr-NH2(RC-121) containing methotrexate attached to the α-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 μg/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 μg/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.
AB - 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-C{A figure is presented}{A figure is presented}s-Thr-NH2(RC-121) containing methotrexate attached to the α-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 μg/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 μg/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.
KW - methotrexate
KW - pancreatic cancer
KW - somatostatin
KW - somatostatin analog carrying cytotoxic radical
UR - http://www.scopus.com/inward/record.url?scp=0026569101&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026569101&partnerID=8YFLogxK
U2 - 10.1016/0304-3835(92)90105-5
DO - 10.1016/0304-3835(92)90105-5
M3 - Article
C2 - 1317746
AN - SCOPUS:0026569101
VL - 62
SP - 263
EP - 271
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 3
ER -