GROWTH INHIBITORY EFFECT OF BESTATIN ON CHORIOCARCINOMA CELL-LINES INVITRO
GROWTH INHIBITORY EFFECT OF BESTATIN ON CHORIOCARCINOMA CELL-LINES INVITRO
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DOI：
10.1007/bf02221328
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发表时间：
1991-10-01
期刊：
影响因子：
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通讯作者：
TOMODA, Y
中科院分区：
文献类型：
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作者：
INO, K;GOTO, S;TOMODA, Y
Bestatin是一种生物反应调节剂（BRM），是氨肽酶B（AP-B）、亮氨酸氨肽酶（Leu）和氨肽酶M（AP-M）的抑制剂。在这份报告中，我们调查了直接影响bestatin对癌细胞的生长在体外使用已建立的四个绒毛膜癌细胞系。琥珀酸脱氢酶抑制试验（SDI）评价体外化疗敏感性。Bestatin对所有绒毛膜癌细胞株均表现出剂量依赖性的生长抑制作用，尤其是对NaUCC-4细胞。对氨基肽酶没有抑制活性的bestatin的异构体（2 R，3S）-AHPA-（R）-Leu和对AP-B具有比bestatin更强的抑制活性的另一种异构体（2S，3S）-AHPA-（R）-Leu对NaUCC-4细胞均不显示生长抑制。因此，bestatin对绒癌细胞的直接作用机制之一可能与抑制AP-B活性而不是抑制AP-M活性有关。此外，放线菌素D对绒毛膜癌细胞的细胞毒性显着增强与bestatin。这些结果表明，bestatin不仅具有间接的宿主介导的抗肿瘤活性，而且对某些类型的癌细胞系具有直接的生长抑制作用。
Bestatin, one of the biological response modifiers (BRMs), is an inhibitor of aminopeptidase B (AP-B), leucine aminopeptidase (LAP) and aminopeptidase M (AP-M). In this report, we investigated the direct effect of bestatin on the growth of cancer cells in vitro using established four choriocarcinoma cell lines. In vitro chemosensitivity was evaluated by the succinate dehydrogenase inhibition (SDI) test. Bestatin showed the growth-inhibitory effect on all the choriocarcinoma cell lines dose-dependently, especially on NaUCC-4 cells. Both an isomer of bestatin with no inhibitory activity against aminopeptidases, (2R, 3S)-AHPA-(R)-Leu, and another isomer with stronger inhibitory activity against AP-B than bestatin, (2S, 3S)-AHPA-(R)-Leu, did not show growth inhibition on NaUCC-4 cells. So it is suggested that one of the possible mechanisms responsible for the direct action of bestatin on the choriocarcinoma cells may be related to the inhibition of activity of LAP or AP-M rather than that of AP-B. Furthermore, cytotoxicity of actinomycin D on the choriocarcinoma cells was significantly enhanced by combination with bestatin. These results suggest that bestatin has not only an indirect host-mediated anti-tumor activity, but also a direct growth-inhibitory effect on some kinds of cancer cell lines.