Molecular changes to HeLa cells on continuous exposure to cisplatin or paclitaxel.
Cancer Chemother Pharmacol
; 58(6): 785-93, 2006 Dec.
Article
em En
| MEDLINE
| ID: mdl-16534613
ABSTRACT
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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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Cisplatino
/
Paclitaxel
/
Resistência a Múltiplos Medicamentos
/
Resistencia a Medicamentos Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Japão