Chen Meiyu, Xiong Fei, Ma Liang, Yao Hong, Wang Qinrong, Wen Lijun, Wang Qian, Gu Ning, Chen Suning
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Soochow University, Suzhou; Collaborative Innovation Center of Hematology, Soochow University, Suzhou.
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing; Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou, People's Republic of China.
Int J Nanomedicine. 2016 Sep 6;11:4413-4422. doi: 10.2147/IJN.S105543. eCollection 2016.
Homoharringtonine (HHT), a natural cephalotaxine alkaloid, has been used in the People's Republic of China for treatment of leukemia for >3 decades. Here, we employed magnetic FeO nanoparticles (MNP-FeO) to improve the therapeutic effect of HHT and investigated its biological effects. Within a certain range of concentrations, the HHT-MNP-FeO showed a more enhanced inhibitory effect on the selected myeloid leukemia cell lines than HHT alone. Compared with HHT, HHT-MNP-FeO could induce more extensive apoptosis in leukemia cells, which also showed more pronounced cell arrests at G0/G1 phase. HHT-MNP-FeO enhanced antitumor activity by downregulating myeloid cell leukemia-1, which could inhibit the activation of caspase-3 and poly-ADP-ribose polymerase. In vivo experiments using tumor-bearing animal models showed that the mean tumor volume with HHT-MNP-FeO was significantly smaller than that with HHT alone (193±26 mm versus 457±100 mm, <0.05), while the mean weight was 0.67±0.03 g versus 1.42±0.56 g (<0.05). Immunohistochemical study showed fewer myeloid cell leukemia-1-stained cells in mice treated with HHT-MNP-FeO than with the controls. These findings provide a more efficient delivery system for HHT in the treatment of hematological malignancy.
高三尖杉酯碱（HHT）是一种天然的三尖杉生物碱，在中华人民共和国已用于治疗白血病超过30年。在此，我们采用磁性FeO纳米颗粒（MNP-FeO）来提高HHT的治疗效果，并研究其生物学效应。在一定浓度范围内，与单独使用HHT相比，HHT-MNP-FeO对所选髓系白血病细胞系显示出更强的抑制作用。与HHT相比，HHT-MNP-FeO可诱导白血病细胞发生更广泛的凋亡，且在G0/G1期的细胞阻滞也更明显。HHT-MNP-FeO通过下调髓系细胞白血病-1增强抗肿瘤活性，髓系细胞白血病-1可抑制半胱天冬酶-3和聚ADP核糖聚合酶的激活。使用荷瘤动物模型进行的体内实验表明，HHT-MNP-FeO组的平均肿瘤体积明显小于单独使用HHT组（193±26 mm对457±100 mm，<0.05），而平均重量分别为0.67±0.03 g对1.42±0.56 g（<0.05）。免疫组织化学研究显示，与对照组相比，接受HHT-MNP-FeO治疗的小鼠中髓系细胞白血病-1染色的细胞更少。这些发现为HHT治疗血液系统恶性肿瘤提供了一种更有效的递送系统。
