Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines.
Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines.
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DOI：
10.1038/bjc.1993.488
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发表时间：
1993-12
影响因子：
8.8
通讯作者：
MITCHELL, JB
中科院分区：
文献类型：
--
作者：
LIEBMANN, JE;COOK, JA;LIPSCHULTZ, C;TEAGUE, D;FISHER, J;MITCHELL, JB
紫杉醇对8种人肿瘤细胞系的细胞毒性已在体外克隆形成试验进行了研究。暴露于2至20 nM紫杉醇浓度24 h后，存活细胞的分数急剧下降;发现紫杉醇IC 50范围为2.5至7.5 nM。然而，将紫杉醇浓度增加到50 nM以上，在药物暴露24小时后没有导致额外的细胞毒性。与用较低浓度的药物处理的细胞相比，在非常高浓度的紫杉醇（10，000 nM）中孵育的细胞的存活率增加。将细胞暴露于紫杉醇的时间从24小时延长至72小时，在不同细胞系中的细胞毒性从5倍增加至200倍。指数生长的细胞对紫杉醇的敏感性高于生长平台期的细胞。Cremophor EL是紫杉醇临床制剂的稀释剂，在浓度为0.135%（v/v）时可拮抗紫杉醇。这些数据表明，当肿瘤长期暴露于紫杉醇时，紫杉醇将在临床上最有效。此外，似乎适度的浓度（即，50 nM）应该与更高浓度的紫杉醇一样有效。最后，我们注意到Cremophor EL是一种生物活性稀释剂，在高浓度（0.135% v/v）下，可以拮抗紫杉醇的细胞毒性。
The cytotoxicity of paclitaxel against eight human tumour cell lines has been studied with in vitro clonogenic assays. The fraction of surviving cells fell sharply after exposure for 24 h to paclitaxel concentrations ranging from 2 to 20 nM; the paclitaxel IC50 was found to range between 2.5 and 7.5 nM. Increasing the paclitaxel concentration above 50 nM, however, resulted in no additional cytotoxicity after a 24 h drug exposure. Cells incubated in very high concentrations of paclitaxel (10,000 nM) had an increase in survival compared with cells treated with lower concentrations of the drug. Prolonging the time of exposure of cells to paclitaxel from 24 to 72 h increased cytotoxicity from 5 to 200 fold in different cell lines. Exponentially growing cells were more sensitive to paclitaxel than were cells in the plateau phase of growth. Cremophor EL, the diluent in which the clinical preparation of paclitaxel is formulated, antagonised paclitaxel at concentrations of 0.135% (v/v). These data suggest that paclitaxel will be most effective clinically when there is prolonged exposure of tumour to the drug. Further, it appears that modest concentrations (i.e., 50 nM) should be as effective as higher concentrations of paclitaxel. Finally, we have noted that Cremophor EL is a biologically active diluent and, at high concentrations (0.135% v/v), can antagonise paclitaxel cytotoxicity.
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影响因子：
64.8
作者：
SCHIFF, PB;FANT, J;HORWITZ, SB
通讯作者：
HORWITZ, SB
DOI：
10.1093/jnci/83.24.1797-a
发表时间：
1991-12-18
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
HOLMES, FA;WALTERS, RS;HORTOBAGYI, GN
通讯作者：
HORTOBAGYI, GN
影响因子：
39.2
作者：
MCGUIRE, WP;ROWINSKY, EK;DONEHOWER, RC
通讯作者：
DONEHOWER, RC
DOI：
10.1016/s0006-291x(05)81474-3
发表时间：
1992-08-31
影响因子：
3.1
作者：
RIOU, JF;NAUDIN, A;LAVELLE, F
通讯作者：
LAVELLE, F
DOI：
10.1111/j.1749-6632.1986.tb38455.x
发表时间：
1986-06-30
影响因子：
5.2
作者：
HORWITZ, SB;LOTHSTEIN, L;ZEHEB, R
通讯作者：
ZEHEB, R