Establishment of multidrug-resistance cell line C(6)/adr and reversal of drug-resistance.
OBJECTIVE
To investigate the mechanism of multidrug resistance (MDR) in a human glioma cell and methods for overcoming multi-drug resistance.


METHODS
MDR cell line C(6)/adr was established. The expression of the mdr-1 gene and its P-glycoprotein (P-gp) in the C(6)/adr cell line was observed by RT-PCR and flow cytometry. The reversal of MDR by verapamil, erythromycin, dihydropyridine, P-gp monoclonal antibody and Salvia miltiorrhiza (SM) was studied by microtiter tetrazolium (MTT) assay or by high performance liquid chromatographic assay.


RESULTS
The mdr-1 gene of the C(6)/adr cell line was positive, over-expressing P-gp. The drug-resistance of the C(6)/adr cell lines could be partly reversed by 2 - 6 microg/ml of verapamil, 50 - 100 microg/ml of erythromycin, or 5 microg/ml of dihydropyridine. As concentration increased, they had a better effect. Among these drugs, 100 microg/ml of erythromycin had the best result of reversal. Dihydropyridine 1 microg/ml, P-gp monoclonal antibody and SM had no effect.


CONCLUSIONS
The mdr-1 gene and its expression might be associated with the MDR of glioma cells. Verapamil, erythromycin and dihydropyridine could reverse the MDR of glioma cells.
Liu
Fusheng
F
Beijing Neurosurgical Institute, Beijing 100050, China. liufuchengs@hotmail.com
Wang
Chongcheng
C
Zhang
Qinglin
Q
Li
Junhua
J
Zhang
Yazhuo
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000276:immunology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002470:Cell Survival / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004917:Erythromycin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D004917:Erythromycin; D004317:Doxorubicin; D014700:Verapamil