Schedule-dependent interactions between pemetrexed and cisplatin in human carcinoma cell lines in vitro
Schedule-dependent interactions between pemetrexed and cisplatin in human carcinoma cell lines in vitro
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DOI：
10.3727/000000006783981215
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发表时间：
2006-01-01
影响因子：
3.1
通讯作者：
Furukawa, Y
中科院分区：
文献类型：
--
作者：
Kano, Y;Akutsu, M;Furukawa, Y
培美曲塞和顺铂的组合显示出对间皮瘤和肺癌的良好临床活性。为了研究潜在的细胞基础，并提供如何优化组合的线索，我们在体外研究了培美曲塞和顺铂对四种人癌细胞系的时间表依赖性细胞毒性作用。将肿瘤细胞与培美曲塞和顺铂以各种时间表孵育24小时。通过等效线图法分析5天后的组合效应。培美曲塞和顺铂同时作用24 h以及顺铂作用24 h后培美曲塞作用24 h均对人肺癌A549、乳腺癌MCF 7和卵巢癌PA 1细胞产生拮抗作用，对结肠癌WiDr细胞产生累加作用。培美曲塞24 h后联合顺铂24 h在MCF 7细胞中产生协同效应，在A549和PA 1细胞中产生累加/协同效应，在WiDr细胞中产生累加效应。MCF 7和PA 1细胞的细胞周期分析支持这些发现。我们的研究结果表明，培美曲塞和顺铂的同时临床给药可能是次优的。培美曲塞联合顺铂在细胞水平上的最佳给药方案是培美曲塞和顺铂序贯给药，该方案值得临床研究。
The combination of pemetrexed and cisplatin shows good clinical activity against mesothelioma and lung cancer. In order to study the potential cellular basis for this, and provide leads as to how to optimize the combination, we studied the schedule-dependent cytotoxic effects of pemetrexed and cisplatin against four human cancer cell lines in vitro. Tumor cells were incubated with pemetrexed and cisplatin for 24 h at various schedules. The combination effects after 5 days were analyzed by the isobologram method. Both simultaneous exposure to pemetrexed and cisplatin for 24 h and sequential exposure to cisplatin for 24 h followed by pemetrexed for 24 It produced antagonistic effects in human lung cancer A549, breast cancer MCF7, and ovarian cancer PA1 cells and additive effects in colon cancer WiDr cells. Pemetrexed for 24 h followed by cisplatin for 24 h produced synergistic effects in MCF7 cells, additive/synergistic effects in A549 and PA1 cells, and additive effects in WiDr cells. Cell cycle analysis of MCF7 and PA1 cells supported these findings. Our results suggest that the simultaneous clinical administration of pemetrexed and cisplatin may be suboptimal. The optimal schedule of pemetrexed in combination with cisplatin at the cellular level is the sequential administration of pemetrexed followed by cisplatin and this schedule is worthy of clinical investigations.