Dual effects of arsenic trioxide (AS2O3) on non-acute promyelocytic leukaemia myeloid cell lines:: induction of apoptosis and inhibition of proliferation
Dual effects of arsenic trioxide (AS2O3) on non-acute promyelocytic leukaemia myeloid cell lines:: induction of apoptosis and inhibition of proliferation
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DOI：
10.1046/j.0007-1048.2001.03298.x
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发表时间：
2002-03-01
影响因子：
6.5
通讯作者：
Schrezenmeier, H
中科院分区：
文献类型：
--
作者：
Rojewski, MT;Baldus, C;Schrezenmeier, H
As 2 O3在复发性急性早幼粒细胞白血病患者中的临床疗效已得到证实。有证据表明，As 2 O3的影响并不局限于APL的特定事件。As 2 O3可能靶向参与其他恶性肿瘤发病机制的机制。我们评估了22个髓系和非髓系恶性肿瘤细胞系对As 2 O3和细胞生长抑制剂诱导凋亡的敏感性。使用浓度为0.01-10 μ mol/l的As 2 O3。细胞株显示不同的动力学响应和不同的敏感性As 2 O3。As_2O_3诱导细胞凋亡的最低浓度为0.1 μ mol/l。高浓度的As 2 O3（5 μ mol/L）诱导细胞凋亡的大部分细胞在所有测试的细胞系。低浓度（1 μ mol/l As 2 O3）诱导NB-4细胞凋亡。HL-60 U-937 CEM HL-60 KG-1a、PBL-985、ML-2和MV-4-11在体外培养35 d后，对HEL、K-562、KG-1和Jurkat的细胞毒性无明显影响。1 μ mol/l As_2O_3处理的HEL的非凋亡群体。K-562，K-562（0.02）。K-562（0.1）和Jurkat显示增殖减少。CEM及其多药耐药衍生物对1 μ mol/l As_2O_3敏感。总之。这些数据表明As 2 O3诱导的细胞凋亡并不局限于具有t（15：17）的细胞系。在体外诱导细胞凋亡的As 2 O3浓度，是在体内输注后耐受良好的As 2 O3剂量。因此，As_2O_3可能是一个合适的治疗剂，恶性肿瘤以外的APL提供了足够的剂量和治疗时间的As_2O_3使用。
Clinical efficacy of As2O3 has been shown in patients with relapsed acute promyelocytic leukaemia APL). There is evidence that the effects of As2O3 are not restricted to events specific for APL. As2O3 might target mechanisms involved in the pathogenesis of other malignancies. We assessed susceptibility to induction of apoptosis, by As2O3 and cytostatics in 22 myeloid and non-myeloid malignant cell lines. As2O3 was used in concentrations of 0.01-10 mumol/l. Cell lines displayed different kinetics of response and different sensitivity to As2O3. The minimum concentration of As2O3 for induction of apoptosis was 0.1 mumol/l. High concentrations of As2O3 (5 mumol/l) induced apoptosis in a large proportion of cells in all cell lines tested. Low (1 mumol/l As2O3) concentrations induced apoptosis in NB-4. HL-60, U-937. CEM, HL-60. KG-1a, PBL-985, ML-2 and MV-4-11, but not in HEL, K-562, KG-1 and Jurkat up to 35 d of incubation, However. the non-apoptotic population of 1 mumol/l As2O3-treated HEL. K-562, K-562 (0.02). K-562(0.1) and Jurkat showed reduced proliferation. CEM as well as its' multidrug-resistant derivatives were sensitive to 1 mumol/l As2O3. In summary. these data demonstrate that As2O3-induced apoptosis is not restricted to cell lines with t(15:17). Apoptosis was induced in vitro by As2O3 concentrations that are achievable in vivo after infusion of well-tolerated As2O3 doses. Thus, As2O3 might be a suitable therapeutic agent for malignancies other than APL provided the adequate dose and duration of As2O3 treatment are used.