高三尖杉酯碱对白血病细胞分化和肿瘤转移的影响

Effect of Homoharringtonine on Leukemia Cell Differentiation and Tumor Metastasis

为研究高三尖杉酯碱（Ｈｏｍ）对白血病细胞分化和肿瘤转移的影响．采用四氮唑蓝法检测ＨＬ－６０细胞的分化及测定游离磷含量观测肿瘤细胞Ｎａ＋－Ｋ＋－ＡＴＰ酶和Ｍｇ＋＋－ＡＴＰ酶活性．肿瘤转移模型采用小鼠皮下接种Ｌｅｗｉｓ肺癌观测肺转移灶数和小鼠足跖接种Ｐ３８８白血病细胞观察动物生存期，且用γ射线测定法评价１２５Ｉ－纤维蛋白原与肿瘤细胞的结合能力．结果显示Ｈｏｍ１．５～４．５μｇ／Ｌ能诱导ＨＬ－６０细胞分化，Ｈｏｍ０．１μｍｏｌ／Ｌ２４ｈ对Ｆｒｉｅｎｄ白血病细胞Ｎａ＋－Ｋ＋－ＡＴＰ酶活性抑制，对Ｍｇ＋＋－ＡＴＰ酶活性无影响，Ｈｏｍ０．５～１．５ｍｇ·ｋｇ－１／ｄ剂量下能抑制Ｌｅｗｉｓ癌肺转移和Ｐ３８８白血病细胞淋巴道转移，以及Ｈｏｍ２～１０ｍｇ／Ｌ抑制纤维蛋白原与癌细胞的结合．

To study the effect of homoharringtonine ( Hom) on leukemia cell differentiation and tumor metastasis. HL 60 cell differentiation was assessed by NBT staining, and Na + K + ATPase activity was determined by measuring dissociated phosphate content. Tumor metastatic assays were used to count pulmonary metastic foci by transplantation of Lewis lung carcinoma ic and observe mouse life span by ic transplanting P388 leukemic cell on foot pad. The binding of 125 I fibrinogen to leukemia cells was also determined by gamma radiospectrometry. It was showed that Hom 1.5￣4.5 μg/L induced the differentiation of human leukemia cell HL 60 and Hom 0.1 μm 24 h inhibited Na + K + ATPase activity, but not Mg ++ ATPase of Friend leukemia cells. Hom 0.5￣1.5 mg·kg -1 /d decreased the pulmonary metastasis of Lewis lung carcinoma and suppressed lympho node metastasis of P388 leukemia. Hom at 2￣10 mg/L blocked the binding of fibrinogen to tumor cells. So it is possible that Hom induces leukemia cell differentiation and exhibits the antimetastatic activity through above mentioned pathways.