Interleukin-1 alpha increases the cytotoxic activity of etoposide against human osteosarcoma cells.
Interleukin-1 alpha increases the cytotoxic activity of etoposide against human osteosarcoma cells.
复制标题
DOI：
10.1046/j.1359-4117.2002.01003.x
复制
发表时间：
2002-01-01
影响因子：
--
通讯作者：
Kleinerman, Eugene S
中科院分区：
文献类型：
--
作者：
Jia, Shu-Fang;Zwelling, Leonard A;Kleinerman, Eugene S
肺转移瘤对挽救化疗耐药的复发仍然是骨肉瘤患者的一个主要问题。我们的目标是确定新的组合生物反应调节剂加上化疗药物，可以转化为临床试验。复发性骨肉瘤患者对依托泊苷的反应率极低。目前的研究表明，IL-1 α显着增加MG-63，SAOS-2和TE-85骨肉瘤细胞对依托泊苷的敏感性时，两种药物同时使用。5.0 U/ml IL-1 α可使1 μ M依托泊苷的细胞抑制活性分别从35%增加到70%、30%增加到65%和4%增加到90%。使用集落形成测定来量化细胞毒性的分析显示，当使用组合治疗时，暴露于依托泊苷后的细胞存活百分比从0.81降低至0.56、从0.55降低至0.2和从0.4降低至0.05。当依托泊苷治疗先于IL-1 α治疗时，未观察到敏感性增加。IL-1 α也增加了这些细胞对阿霉素的敏感性，但对顺铂或托泊替康不敏感。这种增强活性的机制独立于p-糖蛋白、药物摄取或对拓扑异构酶II的影响。
The recurrence of pulmonary metastases resistant to salvage chemotherapy continues to be a major problem in osteosarcoma patients. Our goal is to identify novel combinations of biologic response modifiers plus chemotherapeutic agents that can be translated into clinical trials. Response rates of relapsed osteosarcoma patients to etoposide have been extremely low. The present investigation demonstrated that IL-1 alpha dramatically increased the sensitivity of MG-63, SAOS-2, and TE-85 osteosarcoma cells to etoposide when the two agents were used simultaneously. The cytostatic activity of 1 microM etoposide was increased from 35 to 70%, 30 to 65%, and 4 to 90%, respectively, by 5.0 U/ml IL-1 alpha. Analysis using the colony-forming assay to quantify cytotoxicity showed that the percentage of cell survival following exposure to etoposide decreased from 0.81 to 0.56, 0.55 to 0.2, and 0.4 to 0.05 when the combination treatment was used. Increased sensitivity was not seen when etoposide treatment preceded IL-1 alpha treatment. IL-1 alpha also increased the sensitivity of these cells to doxorubicin but not to cisplatin or topotecan. The mechanism of this enhanced activity is independent of p-glycoprotein, drug-uptake, or effects on topoisomerase II.