| RRC ID |
71654
|
| 著者 |
Shimomura M, Yaoi T, Itoh K, Kato D, Terauchi K, Shimada J, Fushiki S.
|
| タイトル |
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.
|
| ジャーナル |
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.
|
| 巻・号 |
40(4)
|
| ページ |
995-1004
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
II-18(RCB2093)
PC-14(RCB0446)
RERF-LC-KJ(RCB1313) |
