Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by water-soluble chitosan oligomer
Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by water-soluble chitosan oligomer
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DOI：
10.1016/s0145-2126(00)00138-7
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发表时间：
2001-04-01
影响因子：
2.7
通讯作者：
Chung, HT
中科院分区：
文献类型：
--
作者：
Pae, HO;Seo, WG;Chung, HT
水溶性壳聚糖低聚物（WSCO）具有抗肿瘤、免疫增强和抗菌活性。然而，其他生物活性尚不清楚。在此，我们已经证明WSCO能够抑制人白血病HL-60细胞的增殖并诱导这些细胞分化。用WSCO处理4天导致HL-60细胞生长的浓度依赖性降低，如通过细胞计数和MTT测定所测量的。这种效应伴随着G（0）/G（1）细胞比例的显著增加，如流式细胞术所测量的。WSCO还诱导细胞分化，如通过NET的佛波酯依赖性减少所测量的，通过Wright-Giemsa染色所检查的形态学变化和通过流式细胞术分析的CD 11b而不是CD 14的表达，表明HL-60细胞向粒细胞样细胞分化。低剂量WSCO与全反式维甲酸（一种向粒细胞样细胞分化的分化剂）的组合表现出对分化的协同作用。此外，用WSCO处理HL-60细胞6或8天导致诱导凋亡，通过琼脂糖凝胶电泳定性检测和通过Annexin V技术使用流式细胞术定量检测。总的来说，WSCO在治疗髓性白血病方面具有潜力。(C)2001爱思唯尔科技有限公司版权所有。
Water-soluble chitosan oligomer (WSCO) has been reported to have anticancer activity, immune-enhancing effect and antimicrobial activity. However, other biological activities are unknown. Herein, we have shown that WSCO is able to inhibit proliferation of human leukemia HL-60 cells and induce these cells to differentiate. Treatment with WSCO for 4 days resulted in a concentration-dependent reduction in HL-60 cell growth as measured by cell counting and MTT assay. This effect was accompanied by a marked increase in the proportion of G(0)/G(1) cells as measured by flow cytometry. WSCO also induced differentiation of the cells as measured by phorbol ester-dependent reduction of NET, morphological changes as examined by Wright-Giemsa staining and expression of CD11b but not of CD14 as analysed by flow cytometry, indicating differentiation of HL-60 cells toward granulocyte-like cells. A combination of low dose of WSCO with all-trans retinoic acid, a differentiating agent toward granulocyte-like cells, exhibited a synergistic effect on the differentiation. In addition, treatment of HL-60 cells with WSCO for 6 or 8 days resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis and quantitatively by Annexin V technique using flow cytometry. Collectively, there is a potential for WSCO in the treatment of myeloid leukemia. (C) 2001 Elsevier Science Ltd. All rights reserved.