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生长抑素及其环状八肽类似物SMS 201-995作为人急性淋巴细胞白血病和急性髓细胞白血病增殖的抑制剂。

Somatostatin and its cyclic octapeptide analog SMS 201-995 as inhibitors of proliferation of human acute lymphoblastic and acute myeloid leukemia.

作者信息

Santini V, Lamberts S W, Krenning E P, Backx B, Löwenberg B

机构信息

Department of Hematology, University of Florence, Italy.

出版信息

Leuk Res. 1995 Oct;19(10):707-12. doi: 10.1016/0145-2126(95)00041-l.

DOI:10.1016/0145-2126(95)00041-l
PMID:7500646
Abstract

Somatostatin (SS) is a 14 amino acid peptide which is secreted by the hypothalamus and the pancreatic islets. It expresses antiproliferative activity in various organ systems, experiments have suggested effects of SS on hematopoietic cells. Here we present investigations regarding the effect of SS and its analog SMS 201-995 (SMS) on the in vitro proliferation of acute lymphoblastic leukemia (ALL; n = 7 cases), acute myeloid leukemia (AML; n = 21 cases) and chronic lymphocytic leukemia (CLL; n = 2 cases). Both SS and SMS inhibited spontaneous leukemic cell growth in approximately 1/3 of cases (i.e. 7/19). G-CSF stimulated AML cells were inhibited by SMS in 11/21 cases. AML cell proliferation induced by IL-3 or GM-CSF was suppressed in only 3/21 and 6/21 cases, respectively. In ALL cells, IL-7-induced proliferation was suppressed by SMS in 3/7 cases. The effect of SMS seemed to depend on the type of the hematopoietic growth factor, and on their concentrations. In fact, high concentrations of G-CSF could override SMS blocking completely. Colony formation by normal marrow progenitors and DNA synthesis by HL-60 and T11/65 leukemic cell lines were not affected by SMS. In conclusion, somatostatin may act as a negative regulator of the proliferative activity of human leukemia.

摘要

生长抑素(SS)是一种由下丘脑和胰岛分泌的含14个氨基酸的肽。它在各种器官系统中表现出抗增殖活性,实验表明SS对造血细胞有影响。在此,我们展示了关于SS及其类似物SMS 201 - 995(SMS)对急性淋巴细胞白血病(ALL;7例)、急性髓细胞白血病(AML;21例)和慢性淋巴细胞白血病(CLL;2例)体外增殖作用的研究。SS和SMS在大约1/3的病例中(即7/19)抑制白血病细胞的自发生长。在21例中,SMS抑制了G - CSF刺激的AML细胞生长的有11例。由IL - 3或GM - CSF诱导的AML细胞增殖分别仅在3/21和6/21例中受到抑制。在ALL细胞中,SMS在3/7例中抑制了IL - 7诱导的增殖。SMS的作用似乎取决于造血生长因子的类型及其浓度。事实上,高浓度的G - CSF可以完全克服SMS的阻断作用。正常骨髓祖细胞的集落形成以及HL - 60和T11/65白血病细胞系的DNA合成不受SMS影响。总之,生长抑素可能作为人类白血病增殖活性的负调节因子。

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