Accumulation and Photodynamic Activity of Chlorin e6 in Cisplatin-Resistant Human Lung Cancer Cells

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. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 3010-3017, 2011