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在克隆形成试验中研究重组人干扰素α 2与细胞毒性药物的联合作用。

Combined recombinant human interferon alpha 2 and cytotoxic agents studied in a clonogenic assay.

作者信息

Welander C E, Morgan T M, Homesley H D, Trotta P P, Spiegel R J

出版信息

Int J Cancer. 1985 Jun 15;35(6):721-9. doi: 10.1002/ijc.2910350605.

DOI:10.1002/ijc.2910350605
PMID:4008100
Abstract

A human tumor clonogenic assay has been used to test the antiproliferative effect of recombinant human leukocyte interferon alpha 2 alone and in combination with each of 8 cytotoxic agents. Cell lines derived from 6 human tumors and primary tumor cells from 13 patients have been used in these clonogenic assay studies. Results show that interferon as a single agent causes insignificant reduction in tumor cell colony survival if the short-term 1-hr cell exposure method is used; only high concentrations of interferon used in continuous cell exposure in the clonogenic assay can demonstrate a reduction in colony survival to below 50% of control values. Combinations of interferon with either doxorubicin or cisplatin frequently show additive and occasionally synergistic antiproliferative effects on tumor cell colony formation. Variations in drug concentrations and sequencing of drugs have been tested, showing that optimal antiproliferative effects of combined interferon and doxorubicin are realized when maximal concentrations of interferon and prolonged cell exposure time of both interferon and doxorubicin are employed. Combinations of interferon and doxorubicin tested in the clonogenic assay demonstrate cytotoxicity superior to that of either agent tested alone.

摘要

一种人肿瘤克隆形成试验已被用于测试重组人白细胞干扰素α2单独使用以及与8种细胞毒性药物联合使用时的抗增殖作用。这些克隆形成试验研究使用了源自6种人类肿瘤的细胞系和13名患者的原发性肿瘤细胞。结果表明,如果采用短期1小时细胞暴露方法,干扰素作为单一药物只会使肿瘤细胞集落存活率出现微不足道的降低;只有在克隆形成试验中持续细胞暴露时使用高浓度的干扰素,才能使集落存活率降低至对照值的50%以下。干扰素与阿霉素或顺铂联合使用时,对肿瘤细胞集落形成常常显示出相加作用,偶尔还会有协同抗增殖作用。已经测试了药物浓度和给药顺序的变化,结果表明,当使用干扰素的最大浓度以及干扰素和阿霉素都延长细胞暴露时间时,干扰素与阿霉素联合使用能实现最佳抗增殖效果。在克隆形成试验中测试的干扰素与阿霉素联合使用,显示出的细胞毒性优于单独测试的任何一种药物。

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