Taxol effect on cisplatin sensitivity and cisplatin cellular accumulation in human ovarian cancer cells.

Taxol effect on cisplatin sensitivity and cisplatin cellular accumulation in human ovarian cancer cells.
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发表时间:
1993
期刊:
Journal of the National Cancer Institute. Monographs
影响因子:
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通讯作者:
R. Parker;M. Dabholkar;K. B. Lee;F. Bostick-Bruton;E. Reed
R. Parker;M. Dabholkar;K. B. Lee;F. Bostick-Bruton;E. Reed
中科院分区:
其他
文献类型:
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作者:
R. Parker;M. Dabholkar;K. B. Lee;F. Bostick-Bruton;E. Reed

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紫杉醇和顺铂是迄今为止发现的用于治疗晚期卵巢癌的两种最有效的药物。学习如何最好地结合联合收割机这些代理商是临床前和临床研究的重点进行了一些机构。在成对的顺铂敏感的A2780和顺铂耐药的A2780/CP 70人卵巢癌细胞系中研究了泰素对细胞对顺铂敏感性的影响。在用泰素特异性测序的条件下生成顺铂生长曲线,并获得并比较顺铂的IC 50(生长被抑制至对照的50%的浓度)。紫杉醇在所有实验中以IC 10剂量使用。在所有实验中,紫杉醇处理24小时,顺铂处理1小时。二甲基亚砜(DMSO)是所有紫杉醇贮备液的稀释剂。分别测定紫杉醇和DMSO对顺铂细胞蓄积的影响。报告的终点包括细胞毒性和紫杉醇对顺铂细胞蓄积的影响。使用微量培养四唑测定,顺铂的生长曲线,获得紫杉醇的影响下,在紫杉醇剂量为3 nM的两种细胞系。单独的DMSO对肿瘤细胞生长没有影响。在A2780细胞中,紫杉醇对顺铂细胞毒性的影响是适度的,而顺铂诱导的细胞杀伤增强1.5倍时,顺铂后立即给予紫杉醇。在A2780/CP 70细胞中,当在泰素后立即给予顺铂时,泰素使顺铂诱导的细胞杀伤增加30倍;当在泰素完成后24小时给予顺铂时,泰素使顺铂诱导的细胞杀伤增加75倍;当在泰素完成后48小时给予顺铂时,泰素使顺铂诱导的细胞杀伤增加19倍。(250字处删节)
Taxol and cisplatin are the two most effective agents discovered to date for treating advanced-stage cancer of the ovary. Learning how best to combine these agents is the focus of preclinical and clinical studies conducted at a number of institutions. Taxol's effect on cellular sensitivity to cisplatin was studied in paired cisplatin-sensitive A2780 and cisplatin-resistant A2780/CP70 human ovarian cancer cell lines. Cisplatin growth curves were generated under conditions of specific sequencing with Taxol, and IC50s (concentrations at which growth is inhibited to 50% of control) for cisplatin were obtained and compared. Taxol was used at an IC10 dose in all experiments. Taxol treatments were for 24 hours and cisplatin treatments were for 1 hour in all experiments. Dimethyl sulfoxide (DMSO) was the diluent for all Taxol stock solutions. Separately, the effects of Taxol and DMSO on cisplatin cellular accumulation were measured. End points reported include measures of cytotoxicity and Taxol effects on cisplatin cellular accumulation. Using a microculture tetrazolium assay, cisplatin growth curves were obtained under the influence of Taxol, at a Taxol dose of 3 nM for both cell lines. DMSO alone had no effect on tumor cell growth. In A2780 cells, the influence of Taxol on cisplatin cytotoxicity was modest, whereas cisplatin-induced cell kill was augmented 1.5-fold when cisplatin was given immediately after Taxol. In A2780/CP70 cells, Taxol augmented cisplatin-induced cell kill by 30-fold when cisplatin was given immediately after Taxol; 75-fold when cisplatin was given 24 hours after completion of Taxol; and 19-fold when cisplatin was given 48 hours after completion of Taxol.(ABSTRACT TRUNCATED AT 250 WORDS)