title: Accumulation and photodynamic activity of chlorin e6 in cisplatin-resistant human lung cancer cells.
abstract: 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.
authors.affiliation: Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Sayo
authors.initials: S
authors.lastname: Horibe
authors.forename: Junya
authors.initials: J
authors.lastname: Nagai
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yumoto
authors.forename: Riichi
authors.initials: R
authors.lastname: Tawa
authors.forename: Mikihisa
authors.initials: M
authors.lastname: Takano
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D017319:Photosensitizing Agents / Q000378:metabolism* / Q000494:pharmacology*; D011166:Porphyrins / Q000378:metabolism* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013696:Temperature; D013997:Time Factors
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D002945:Cisplatin; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D017319:Photosensitizing Agents; D011166:Porphyrins; D012333:RNA, Messenger; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C475446:chlorin e4; C421109:multidrug resistance-associated protein 1