RRC ID 71654
Author Shimomura M, Yaoi T, Itoh K, Kato D, Terauchi K, Shimada J, Fushiki S.
Title Drug resistance to paclitaxel is not only associated with ABCB1 mRNA expression but also with drug accumulation in intracellular compartments in human lung cancer cell lines.
Journal Int J Oncol
Abstract In order to clarify the mechanisms of resistance to paclitaxel in lung cancer, three human lung cancer cell lines which exhibit different sensitivity to paclitaxel were investigated from the following viewpoints: overexpression of ATP-binding cassette, sub-family B, member 1 (ABCB1), mutations on paclitaxel binding site of β-tubulin genes, quantity of polymerized tubulin and the intracellular localization of paclitaxel. ABCB1 expression was evaluated by real-time RT-PCR. No correlations were noted between the ABCB1 expression in the sensitive and resistant cell lines at the mRNA level. No mutations on the paclitaxel binding site of the β-tubulin genes were detected in either the resistant or sensitive cells. Live cell images obtained by confocal laser microscopy revealed that the resistant cell line, RERF-LC-KJ, had more accumulation of Oregon Green® 488 conjugated paclitaxel in the lysosomal and extra-lysosomal compartments of cytoplasm than other cell lines. The results obtained in this study indicated that the changes in the subcellular localization could contribute to the production of paclitaxel resistance in lung cancer cell lines. Further studies should be conducted to elucidate the molecular mechanisms that differentiate the intracellular localization of paclitaxel.
Volume 40(4)
Pages 995-1004
Published 2012-4-1
DOI 10.3892/ijo.2011.1297
PMID 22179563
PMC PMC3584812
MeSH ATP Binding Cassette Transporter, Subfamily B ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics* Acetylation Antineoplastic Agents, Phytogenic / pharmacokinetics Antineoplastic Agents, Phytogenic / pharmacology Binding Sites Carcinoma, Non-Small-Cell Lung / drug therapy* Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / metabolism* Cell Line, Tumor Drug Resistance, Neoplasm Humans Lung Neoplasms / drug therapy* Lung Neoplasms / genetics Lung Neoplasms / metabolism* Microscopy, Confocal Paclitaxel / pharmacokinetics Paclitaxel / pharmacology* Point Mutation RNA, Messenger / biosynthesis* RNA, Messenger / genetics Tubulin / genetics Tubulin / metabolism
IF 3.899
Human and Animal Cells II-18(RCB2093) PC-14(RCB0446) RERF-LC-KJ(RCB1313)