Effects of selective somatostatin analogs and cortistatin on cell viability in cultured human non-functioning pituitary adenomas.
Clinically "non-functioning" human pituitary adenomas (NFPA) constitute about 35% of pituitary adenomas. Somatostatin receptors (SSTR) expression in these adenomas has previously been described both in vitro and in vivo, without evidence for a correlation with tumor volume or the therapeutic efficacy of somatostatin analogs. This study was performed on 13 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". In addition, 3 growth hormone (GH)-secreting adenomas served as controls. A specimen from each tumor was dispersed and digested to isolate and culture the tumor cells, and the in vitro effects of SSTR2 and SSTR5 selective analogs and Cortistatin (CST) (100nM) on cell viability were studied. The quantity of viable cells was estimated using the XTT method. RNA purification of tumor samples and subsequent RT-PCR studies for SSTR2 and SSTR5 expression were performed. Somatostatin analog with high affinity for SSTR2 reduced cell viability by 20-80% in 8 of 13 NFPAs studied, all expressing the SSTR2. The inhibitory effect on cell viability of SSTR5-selective analog was 15-80% in 10 of 13 NFPAs studied, all but three expressing the SSTR5. CST, however, effectively reduced cell viability in only 6 NFPAs. Cell viability was inhibited by all peptides studied in 2 out of 3 GH-secreting adenomas, expressing both receptors. The third adenoma responded to SSTR2 analog and expressed only SSTR2. These results suggest the involvement of SSTR2 and SSTR5 in the anti-proliferative effects of somatostatin; however, CST is less potent in reducing cell viability in these tumors.
Padova
H
H
Institute of Endocrinology, Rabin Medical Center, Petah-Tiqva, Tel Aviv University, Sackler School of Medicine, Israel.
Rubinfeld
H
H
Hadani
M
M
Cohen
Z R
ZR
Nass
D
D
Taylor
J E
JE
Culler
M D
MD
Shimon
I
I
D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism / Q000473:pathology; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D009479:Neuropeptides; D010456:Peptides, Cyclic; C467796:cortistatin 14; D019382:Human Growth Hormone; D013004:Somatostatin