Characterization and modulation of drug resistance of human paediatric rhabdomyosarcoma cell lines

Citation
Ha. Cocker et al., Characterization and modulation of drug resistance of human paediatric rhabdomyosarcoma cell lines, BR J CANC, 83(3), 2000, pp. 338-345
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
BRITISH JOURNAL OF CANCER
ISSN journal
0007-0920 → ACNP
Volume
83
Issue
3
Year of publication
2000
Pages
338 - 345
Database
ISI
SICI code
0007-0920(200008)83:3<338:CAMODR>2.0.ZU;2-J
Abstract
The role of multidrug resistance (MDR) and p53 functional status in the tre atment of paediatric rhabdomyosarcoma is unclear. We have characterized a p anel of seven human rhabdomyosarcoma cell lines for MDR and p53 phenotype. None of the cell lines had P-glycoprotein (P-gp) or multidrug resistance-re lated protein (MRP) detectable by Western blotting, whereas immunohistochem istry suggested that very low levels of MDR proteins may be present in some of the lines, RT-PCR studies indicated that mdr-1, mrp-1 and Irp mRNA was present in 5/7, 7/7 and 5/7 lines respectively. The function of p53 is comp romised in six of the lines, either through mutation of the p53 gene or by overexpression of mdm-2. The sensitivity of many of the cell lines to vincr istine could be modulated above 2-fold and as high as 16-fold using two mod ulating agents, PSC833 and VX710 (with VX710 being a significantly more pot ent modulator of the rhabdomyosarcoma lines). PSC833 also increased vincris tine accumulation in all of the lines from 1.2- to 2.2-fold. These results suggest that some of these cell lines have low levels of multidrug resistan ce. The level of MDR proteins is very low and therefore difficult to detect , but may be sufficient to confer low-level, but clinically relevant, resis tance to some cytotoxic agents, especially vincristine. These cell lines wi ll therefore provide a suitable model to test new strategies in treatment a nd for further understanding relationships between protein expression and d rug resistance. (C) 2000 Cancer Research Campaign.