| Molecular changes to HeLa cells on continuous exposure to cisplatin or paclitaxel. | |
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MedLine Citation:
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PMID: 16534613 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To achieve a reversal of multidrug resistance (MDR) in cancer chemotherapy, it is crucial to clarify the characteristics of MDR cells generated by various types of chemotherapeutic agents and to find novel targets. METHODS: Cisplatin- and paclitaxel-resistant HeLa sublines (HeLa/CDDP and HeLa/TXL, respectively) were established by continuous exposure and their cellular changes were examined based on growth inhibition assays, the transport activity of P-glycoprotein/MDR1, and a RT-PCR analysis of MDR-related factors. RESULTS: HeLa/CDDP cells showed cross-resistance to platinum derivatives, whereas HeLa/TXL cells were resistant to a variety of MDR1 substrates. Transport activity of MDR1 was reduced in HeLa/CDDP cells and the expression of MDR1 was significantly accelerated in HeLa/TXL cells, compared with HeLa cells. In addition, the expression levels of MDR-related transporters (MRP1-5 or BCRP), betatubulin which is a target for taxanes, and apoptosis-regulated factors were comparable among the three cell lines. On the other hand, the mRNA levels of gamma-glutamyl transferase, but not gamma-glutamyl cysteine synthetase, were higher in HeLa/CDDP cells than in HeLa and HeLa/TXL cells. CONCLUSIONS: HeLa/CDDP cells showed decreased activity and expression of MDR1 and overexpression of gamma-GT but not gamma-GCS whereas the activity of MDR1 in HeLa/TXL cells was significantly enhanced. Thus, the molecular changes to HeLa cells caused by continuous exposure to cisplatin or paclitaxel were in part clarified, and therefore an understanding of the cellular changes induced by chemotherapeutic agents will be necessary to establish a strategy for reversing MDR. |
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Authors:
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Kohji Takara; Yukihisa Obata; Eri Yoshikawa; Noriaki Kitada; Toshiyuki Sakaeda; Noriaki Ohnishi; Teruyoshi Yokoyama |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-03-14 |
Journal Detail:
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Title: Cancer chemotherapy and pharmacology Volume: 58 ISSN: 0344-5704 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-09-05 Completed Date: 2007-01-03 Revised Date: 2009-04-20 |
Medline Journal Info:
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Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 785-93 Citation Subset: IM |
Affiliation:
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Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, 607-8414, Kyoto, Japan. takara@mb.kyoto-phu.ac.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics Antineoplastic Agents / pharmacology Cell Proliferation / drug effects Cisplatin / pharmacology* Cyclosporine / pharmacology Drug Resistance, Multiple / genetics* Drug Resistance, Neoplasm / genetics* Gene Expression Regulation, Neoplastic / drug effects, genetics Glutamate-Cysteine Ligase / genetics Hela Cells Humans Inhibitory Concentration 50 Multidrug Resistance-Associated Proteins / genetics Neoplasm Proteins / genetics P-Glycoprotein / genetics Paclitaxel / pharmacology* Proto-Oncogene Proteins c-bcl-2 / genetics RNA, Messenger / genetics, metabolism Receptors, Steroid / genetics Reverse Transcriptase Polymerase Chain Reaction Tubulin / genetics bcl-2-Associated X Protein / genetics gamma-Glutamyltransferase / genetics |
| Chemical | |
Reg. No./Substance:
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0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Antineoplastic Agents; 0/Multidrug Resistance-Associated Proteins; 0/Neoplasm Proteins; 0/P-Glycoprotein; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/Receptors, Steroid; 0/Tubulin; 0/bcl-2-Associated X Protein; 0/pregnane X receptor; 15663-27-1/Cisplatin; 33069-62-4/Paclitaxel; 59865-13-3/Cyclosporine; EC 2.3.2.2/gamma-Glutamyltransferase; EC 6.3.2.2/Glutamate-Cysteine Ligase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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