Effect of somatostatin and tamoxifen on the growth of human pancreatic cancers in nude mice.
We studied the effects of SMS 201-995 (SMS), a somatostatin analog, and tamoxifen, an antagonist of estrogenic actions, on the growth of human pancreatic cancers (SKI and PGER) in vivo. Male nude mice were inoculated with either SKI or PGER by passage of tumor chunks (3 mm2) to the scapular region. Mice from each tumor group were randomly allocated to one of four treatment groups: group 1, control group; group 2, SMS (100 micrograms/kg t.i.d.); group 3, tamoxifen (10 mg/kg three times a week); and group 4, SMS (100 micrograms/kg t.i.d.) + tamoxifen (10 mg/kg three times a week). The somatostatin analog, SMS, given alone or as a combined regimen with tamoxifen, significantly reduced (a) the rate of growth of SKI, and (b) DNA, RNA, and protein content of the tumors. On the other hand, in the case of PGER tumors, none of the treatment regimens significantly influenced the growth of PGER in vivo. Despite showing no significant effects during the study, PGER tumors in mice receiving tamoxifen alone had significantly lower total DNA, RNA, and protein contents compared to control tumors; this was reversed on combined treatment with SMS. None of the growth parameters of PGER was effected by SMS alone. We conclude that, in the case of SKI, SMS with or without tamoxifen was effective as a growth inhibitory agent, whereas in the case of PGER, tamoxifen alone was effective. This finding suggests that independent pathways mediate the growth-inhibitory effects of tamoxifen and SMS, and that different pancreatic cancers may respond to the two agents differently, some with inhibition, some not.
Poston
G J
GJ
Department of Surgery University of Texas Medical Branch, Galveston 77550.
Townsend
C M
CM
Rajaraman
S
S
Thompson
J C
JC
Singh
P
P
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000187:drug effects; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000187:drug effects; D013629:Tamoxifen / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D013629:Tamoxifen; D015282:Octreotide