Imamura N, Kimura A
Department of Hematolgoy and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Leuk Lymphoma. 2000 May;37(5-6):663-7. doi: 10.3109/10428190009058523.
Ubenimex (Bestatin), a low-molecular-mass dipeptide, has been demonstrated to have anti-tumor activities and immunomodulating activities. We here report cell growth inhibition and phenotypic changes of HL-60 and HL-60R cell lines induced by Bestatin treatment. Bestatin (0.1 microg/ml) showed remarkable cell growth inhibition against HL-60 cells, whereas it was ineffective for HL 60R cells. Bestatin also showed growth inhibition in the concentration of 1 microg/ml against HL-60R cells which are resistant to differentiation induction by DMSO and TPA. In both cell types, the effect of growth inhibition by Bestatin treatment was dose dependent. We found a low level expression of CD13 and a low number of CD13 positive cells in HL-60R cells compared with that of HL-60. We also observed phenotypic changes of HL-60 and HL-60R cells following incubation with Bestatin (10 microg/ml) for 1 and 3 hrs, respectively. With HL-60 cells, the upregulation of CD13/aminopeptidase N was found after 1 hr, however, the downregulation was observed after 3 hrs incubation with Bestatin. On the other hand, the downregulation of CD15 and CD33 was observed after both one and 3 hrs incubation. Similarly, in HL-60R cells, the upregulation of CD13/aminopeptidase N was found temporarily (1hr), and then CD13 downregulation was observed after 3 hrs incubation with Bestatin. No notable change was observed for expression of other myeloid-related antigens, e.g. CD14 (My4, LeuM3), CD11b (OKM1), and CD34 (My10). On the basis of these observations of in vitro activity, we suggest that Bestatin may also be an effective anti-leukemic agent in vivo.
乌苯美司（抑氨肽酶B）是一种低分子量二肽，已被证明具有抗肿瘤活性和免疫调节活性。我们在此报告抑氨肽酶B处理诱导的HL-60和HL-60R细胞系的细胞生长抑制及表型变化。抑氨肽酶B（0.1微克/毫升）对HL-60细胞显示出显著的细胞生长抑制作用，而对HL-60R细胞无效。抑氨肽酶B在1微克/毫升浓度时对抵抗二甲基亚砜和佛波酯诱导分化的HL-60R细胞也显示出生长抑制作用。在两种细胞类型中，抑氨肽酶B处理的生长抑制作用均呈剂量依赖性。我们发现与HL-60相比，HL-60R细胞中CD13表达水平较低且CD13阳性细胞数量较少。我们还分别观察了用抑氨肽酶B（10微克/毫升）孵育1小时和3小时后HL-60和HL-60R细胞的表型变化。对于HL-60细胞，孵育1小时后发现CD13/氨肽酶N上调，但与抑氨肽酶B孵育3小时后观察到下调。另一方面，孵育1小时和3小时后均观察到CD15和CD33下调。同样，在HL-60R细胞中，暂时（1小时）发现CD13/氨肽酶N上调，然后与抑氨肽酶B孵育3小时后观察到CD13下调。其他髓系相关抗原如CD14（My4，LeuM3）、CD11b（OKMl）和CD34（My10）的表达未观察到明显变化。基于这些体外活性观察结果，我们认为抑氨肽酶B在体内可能也是一种有效的抗白血病药物。
