Schwab R E, Froidevaux S, Paku S, Tejeda M, Szende B, Pap A, Beglinger C, Eberle A N, Kéri G
3rd Department of Medicine MAV Hospital, Podmaniczky u. 111, H-1062 Budapest, Hungary.
Anticancer Res. 2001 Jan-Feb;21(1A):71-5.
TT-232, a somatostatin analogue, induces apoptosis in various tumours. The aim of our study was to characterise its effect on human melanoma cells and tumours.
Proliferation of seven melanoma cell lines was tested in vitro with the methylene blue test. D10 and 205 cells were also implanted into CB17-scid mice which received 30-150-750 micrograms/kg/day of TT-232 or saline. Animals with 205 cells received twice-daily subcutaneous injections whereas animals with D10 cells were treated with osmotic mini-pumps. In addition, TT-232 metabolites were generated with tissue homogenates and tested in vitro.
TT-232 strongly inhibited proliferation of all cell lines in vitro and tumour growth in vivo. Two out of 8 animals (30-150 micrograms/kg) in the 205 model and one out of 8(150 micrograms/kg) in the D10 model became completely tumour-free at the 11th and 9th day of treatment, respectively. TT-232 was degraded only by liver homogenate whilst its metabolite had no antiproliferative effect in vitro.
TT-232 is a promising drug candidate for melanoma.
生长抑素类似物TT - 232可诱导多种肿瘤细胞凋亡。本研究旨在明确其对人黑色素瘤细胞和肿瘤的作用。
采用亚甲蓝试验在体外检测7种黑色素瘤细胞系的增殖情况。将D10和205细胞接种到CB17 - scid小鼠体内,这些小鼠接受30 - 150 - 750微克/千克/天的TT - 232或生理盐水。接种205细胞的动物接受每日两次皮下注射,而接种D10细胞的动物用渗透微型泵进行治疗。此外,用组织匀浆生成TT - 232代谢产物并进行体外检测。
TT - 232在体外强烈抑制所有细胞系的增殖以及体内肿瘤的生长。在205模型中,8只动物中有2只(30 - 150微克/千克)在治疗第11天完全无瘤,在D10模型中,8只动物中有1只(150微克/千克)在治疗第9天完全无瘤。TT - 232仅被肝脏匀浆降解,而其代谢产物在体外无抗增殖作用。
TT - 232是一种有前景的黑色素瘤候选药物。