Growth inhibition of MXT mammary carcinoma by enhancing programmed cell death (apoptosis) with analogs of LH-RH and somatostatin.
BDF female mice inoculated with MXT mammary adenocarcinoma were treated for 30 days with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist D-Trp-6-LH-RH (releasing 25 micrograms/day for 30 days), microcapsules of the somatostatin agonist RC-160 (liberating 25 micrograms/day for one month), or the combination of these peptides. Bilateral surgical ovariectomy was performed in one group which served as an additional control. Tumor volume was measured weekly during the treatment period of 30 days. When tumor volume changes in the treated groups were compared to the corresponding changes in controls, the combination of D-Trp-6-LH-RH and RC-160 was the most effective in inhibiting tumor growth and approached the effect of surgical ovariectomy. At the conclusion of the experiment, tumor weights were also measured. All peptide analogs inhibited tumor weight by 42 to 63%. In the D-Trp-6-LH-RH treated group, ovarian weights and uterine weights decreased by 48% and 52%, respectively, as compared to controls. Histologically, the regressive changes in tumors caused by the treatment with RC-160, D-Trp-6-LH-RH and their combination were characterized by the coexistence of apoptosis (programmed cell death) and coagulation necrosis. The transition of apoptosis into coagulation necrosis was a common finding. The term 'apoptotic index' is proposed for the ratio of tumorous glands containing apoptotic cells. The apoptotic index was higher in the treated groups than in the control.
Szende
B
B
Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, LA.
Lapis
K
K
Redding
T W
TW
Srkalovic
G
G
Schally
A V
AV
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007986:Luteinizing Hormone / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D011869:Radioligand Assay; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014599:Uterus / Q000187:drug effects
D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; D007986:Luteinizing Hormone