Document Detail

Molecular changes to HeLa cells on continuous exposure to cisplatin or paclitaxel.
MedLine Citation:
PMID:  16534613     Owner:  NLM     Status:  MEDLINE    
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.
Kohji Takara; Yukihisa Obata; Eri Yoshikawa; Noriaki Kitada; Toshiyuki Sakaeda; Noriaki Ohnishi; Teruyoshi Yokoyama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-14
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  58     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-09-05     Completed Date:  2007-01-03     Revised Date:  2009-04-20    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  785-93     Citation Subset:  IM    
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, 607-8414, Kyoto, Japan.
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MeSH Terms
ATP-Binding Cassette Transporters / 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
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
Reg. No./Substance:
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; EC Ligase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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