Abstract | PURPOSE: METHODS: BCRP levels and its function were evaluated by Western blotting and flowcytometry, respectively. Gefitinib-insensitive NSCLC cells expressed various levels of BCRP, which were closely correlated not only with the IC50 values of SN-38 (r=0.874, P<0.05) and those of topotecan (r=0.968, P<0.001), but also with the reversal effects of 1 microM gefitinib on SN-38 resistance (r=0.956, P<0.001) and topotecan resistance (r=0.977, P=0.0001). RESULTS: CONCLUSIONS: These findings suggest that BCRP is the most important molecule responsible for topoisomerase I inhibitor resistance, and that the development of BCRP inhibitors is an effective approach for overcoming this resistance. In addition, the examination of BCRP levels in NSCLC tissues may identify an optimal patient population for treatment with topoisomerase I inhibitors alone or in combination with BCRP inhibitors.
|
Authors | Seiji Nagashima, Hiroshi Soda, Mikio Oka, Takeshi Kitazaki, Ken Shiozawa, Yoichi Nakamura, Masaaki Takemura, Hikaru Yabuuchi, Minoru Fukuda, Kazuhiro Tsukamoto, Shigeru Kohno |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 58
Issue 5
Pg. 594-600
(Nov 2006)
ISSN: 0344-5704 [Print] Germany |
PMID | 16520985
(Publication Type: Journal Article)
|
Chemical References |
- ABCG2 protein, human
- ATP Binding Cassette Transporter, Subfamily G, Member 2
- ATP-Binding Cassette Transporters
- Antineoplastic Agents
- Neoplasm Proteins
- Protein Kinase Inhibitors
- Quinazolines
- RNA, Messenger
- Topoisomerase I Inhibitors
- Irinotecan
- Topotecan
- ErbB Receptors
- Adenosine Triphosphatases
- Gefitinib
- Camptothecin
|
Topics |
- ATP Binding Cassette Transporter, Subfamily G, Member 2
- ATP-Binding Cassette Transporters
(genetics, metabolism)
- Adenosine Triphosphatases
(metabolism)
- Antineoplastic Agents
(pharmacology)
- Blotting, Western
- Camptothecin
(analogs & derivatives, metabolism, pharmacology)
- Carcinoma, Non-Small-Cell Lung
(genetics, metabolism, pathology)
- Cell Line, Tumor
- Dose-Response Relationship, Drug
- Drug Resistance, Neoplasm
- ErbB Receptors
(antagonists & inhibitors, genetics, metabolism)
- Flow Cytometry
(methods)
- Gefitinib
- Gene Expression
(drug effects)
- Humans
- Irinotecan
- Lung Neoplasms
(genetics, metabolism, pathology)
- Neoplasm Proteins
(genetics, metabolism)
- Protein Kinase Inhibitors
(pharmacology)
- Quinazolines
(pharmacology)
- RNA, Messenger
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
(methods)
- Spectrometry, Fluorescence
(methods)
- Topoisomerase I Inhibitors
- Topotecan
(metabolism, pharmacology)
|