Schedule-dependent cytotoxicity of methotrexate and 5-fluorouracil in human colon and breast tumor cell lines.

Schedule-dependent cytotoxicity of methotrexate and 5-fluorouracil in human colon and breast tumor cell lines.
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甲氨蝶呤和 5-氟尿嘧啶在人结肠和乳腺肿瘤细胞系中的时间表依赖性细胞毒性。

DOI:
10.1172/jci109946
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发表时间:
1980
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Cadman,E
Cadman,E
中科院分区:
--
文献类型:
--
作者:
Benz,C;Schoenberg,M;Choti,M;Cadman,E

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研究了连续使用甲氨蝶呤和 5-氟尿嘧啶对人结肠腺癌细胞 HCT-8 和激素依赖性人乳腺癌细胞 47-DN 克隆生长的影响。在这两种细胞系中,当在 24 小时甲氨蝶呤暴露期的最后 6 小时内给予 5-氟尿嘧啶时,对克隆生长有显着的协同抑制作用。较短的间隔或相反的药物顺序要么是相加的,要么是拮抗的。这些结果表明药物序列和给药之间的时间间隔对于这些人类细胞系中最佳细胞毒性的重要性。该信息表明,在 5-氟尿嘧啶治疗前 18 小时给予甲氨蝶呤可能在这些恶性肿瘤的临床试验设计中具有潜在的应用。
The effect of sequential methotrexate and 5-fluorouracil on the clonal growth of the human colon adenocarcinoma cell, HCT-8, and the hormone-dependent human breast carcinoma cell, 47-DN, was examined. In both cell lines, when 5-fluorouracil was given during the last 6 h of a 24 h methotrexate exposure period, there was marked synergistic inhibition of clonal growth. Shorter intervals or the reverse sequence of drugs were either additive or antagonistic. These results indicate the importance of the drug sequence and time interval between drug administration for optimal cytotoxicity in these human cell lines. This information suggests that the administration of methotrexate 18 h before 5-fluorouracil may have potential application in the design of clinical trials for these malignancies.