Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
J Pharm Sci. 2011 Jul;100(7):3010-7. doi: 10.1002/jps.22501. Epub 2011 Jan 27.
Cisplatin or cis-diamminedichloroplatinum (II) (CDDP) is one of the most potent anticancer drugs, but the emergence of acquired resistance to CDDP is a major problem in clinical settings. The purpose of this study was to investigate and compare the cellular accumulation and photodynamic activity of chlorin e6, a photosensitizer, in human lung cancer A549 cell line and its CDDP-resistant subline. First, we established the CDDP-resistant (A549/CDDP) cell subline with fourfold greater half-maximal inhibitory concentration value of CDDP on cell growth than that of the parent A549 cells. The cellular accumulation of chlorin e6 was temperature sensitive, and there were no significant differences in chlorin e6 accumulation between the two cell lines. The mRNA expression levels of ABCC1, ABCC2, and ABCG2 in A549/CDDP cells were comparable to those in A549 cells, whereas ABCB1 mRNA level was significantly higher in A549/CDDP cells than in A549 cells. In consistent with chlorin e6 accumulation, chlorin e6-mediated photodynamic activity on A549/CDDP cells was similar to that on A549 cells, whereas no cytotoxicity was observed when these cell lines were kept in dark. Our observations suggest that CDDP resistance has no significant influence on accumulation and photodynamic activity of chlorin e6 in A549 cells.
顺铂或顺式-二氨二氯铂（II）（CDDP）是最有效的抗癌药物之一，但在临床环境中，CDDP 获得性耐药的出现是一个主要问题。本研究旨在研究和比较氯[e6]，一种光敏剂，在人肺癌 A549 细胞系及其 CDDP 耐药亚系中的细胞积累和光动力活性。首先，我们建立了 CDDP 耐药（A549/CDDP）细胞亚系，其对细胞生长的 CDDP 半最大抑制浓度值是亲本 A549 细胞的四倍。氯[e6]的细胞积累对温度敏感，两种细胞系之间氯[e6]的积累没有显著差异。A549/CDDP 细胞中 ABCC1、ABCC2 和 ABCG2 的 mRNA 表达水平与 A549 细胞相当，而 ABCB1 mRNA 水平在 A549/CDDP 细胞中明显高于 A549 细胞。与氯[e6]积累一致，氯[e6]介导的 A549/CDDP 细胞的光动力活性与 A549 细胞相似，而当这些细胞系在黑暗中保持时，没有观察到细胞毒性。我们的观察表明，CDDP 耐药对 A549 细胞中氯[e6]的积累和光动力活性没有显著影响。
