title: Possible involvement of multidrug-resistance-associated protein (MRP) gene expression in spontaneous drug resistance to vincristine, etoposide and adriamycin in human glioma cells.
abstract: The multidrug-resistance phenotype in human tumors is partly associated with over-expression of the 170 kDa-P-glycoprotein encoded by the multidrug-resistance-1 (MDR1) gene. Another related, but non-P-glycoprotein, multidrug-resistance-associated protein (MRP) gene encodes a 190 kDa-membrane ATP-binding protein. Glioblastoma multiforme is a highly malignant primary neoplasm of the central nervous system which is refractory to anti-cancer chemotherapy, but the mechanism underlying this drug resistance is unknown. Out of glioma cell lines, 2, namely IN500 and T98G, which had elevated MRP mRNA levels, showed the highest resistance to multiple anti-cancer agents such as etoposide, vincristine and adriamycin, and decreased intracellular accumulation of etoposide. In the remaining 5 cell lines, various degrees of sensitivity to adriamycin and etoposide appeared to correlate with their respective MRP mRNA levels. Our study proposes that MRP may be involved in spontaneous multidrug resistance in human gliomas.
authors.affiliation: Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: S
authors.initials: S
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Taniguchi
authors.forename: A
authors.initials: A
authors.lastname: Yokomizo
authors.forename: T
authors.initials: T
authors.lastname: Kuwano
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Hori
authors.forename: K
authors.initials: K
authors.lastname: Kohno
authors.forename: M
authors.initials: M
authors.lastname: Kuwano
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D015152:Blotting, Northern; D015139:Blotting, Southern; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000493:pharmacokinetics / Q000494:pharmacology; D015870:Gene Expression; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin