Chang T T, Gulati S, Chou T C, Colvin M, Clarkson B
Cancer Res. 1987 Jan 1;47(1):119-22.
The development of suitable methods for purging the malignant cells contaminating the bone marrow of patients with cancer may offer a better chance of success for autologous bone marrow transplantation. In this paper, we further describe our efforts at purging acute myelogenous leukemia cells. HL-60, a promyelocytic leukemia cell line, was used as a model. 4-Hydroperoxycyclophosphamide (4-HC), VP-16-213 (VP-16), and Adriamycin were used alone or in combination to develop the best method to purge HL-60 cells. The cytotoxicity of 29.2 micrograms/ml (100 microM) of 4-HC was 99.8 +/- 0.12% (SD) on HL-60 cells and 82.5% on colony forming units-granulocyte, macrophage. Ninety-nine % of HL-60 cells and 72.7% of colony forming units-granulocyte, macrophage were inhibited by VP-16 at a concentration of 25 micrograms/ml (42.5 microM). The cytotoxicity of 1.5 micrograms/ml (2.76 microM) of Adriamycin on HL-60 cells was 98.6 +/- 0.8% and inhibited colony forming units-granulocyte, macrophage by 50.8%. The cytotoxicity and interactions of any two drug combinations at different combination ratios and the different effect levels were quantitatively determined by median effect plot and the multiple drug effect equation (T-C. Chou and P. Talalay. Adv. Enzyme Regul. 22: 27-55, 1984). The combination of 4-HC and VP-16 at a 4-HC:VP-16 drug ratio of 1:0.342 was found to be the best for selective toxicity towards HL-60 cells and was superior to the 4-HC-Adriamycin or VP-16 Adriamycin combination for usefulness in purging bone marrow.
开发合适的方法清除癌症患者骨髓中污染的恶性细胞，可能会为自体骨髓移植带来更好的成功机会。在本文中，我们进一步描述了我们清除急性髓性白血病细胞的努力。HL-60，一种早幼粒细胞白血病细胞系，被用作模型。单独或联合使用4-氢过氧环磷酰胺（4-HC）、依托泊苷（VP-16-213，简称VP-16）和阿霉素，以开发清除HL-60细胞的最佳方法。29.2微克/毫升（100微摩尔）的4-HC对HL-60细胞的细胞毒性为99.8±0.12%（标准差），对集落形成单位-粒细胞、巨噬细胞的细胞毒性为82.5%。浓度为25微克/毫升（42.5微摩尔）的VP-16可抑制99%的HL-60细胞和72.7%的集落形成单位-粒细胞、巨噬细胞。1.5微克/毫升（2.76微摩尔）的阿霉素对HL-60细胞的细胞毒性为98.6±0.8%，并抑制集落形成单位-粒细胞、巨噬细胞50.8%。通过中位效应图和多药效应方程（T-C.周和P.塔拉莱。《酶调节进展》22:27-55，1984）定量测定了不同组合比例和不同效应水平下任意两种药物组合的细胞毒性和相互作用。发现4-HC与VP-16的药物比例为1:0.342的组合对HL-60细胞具有最佳的选择性毒性，并且在清除骨髓方面优于4-HC-阿霉素或VP-16-阿霉素组合。
