Reversal of drug resistance mediated by hammerhead ribozyme against multidrug resistance-associated protein 1 in a human glioma cell line.
We examined the effects of suppressing multidrug resistance-associated protein 1 (MRP1) gene expression in a human glioma cell line U87MG. Hammerhead ribozymes, designed to cleave MRP1 mRNA (alphaMRP1-Rz), were transfected into the U87MG cells. The U87MG/alphaMRP1-Rz cells were significantly sensitive to nitrosourea (ACNU) and doxorubicin (DOX) compared with the U87MG cells (p<0.01 and p<0.05, respectively, unpaired t-test). There was no significant difference in the expression of other human genes between the U87MG/alphaMRP1-Rz and controls by cDNA array. The hammerhead ribozyme-mediated specific suppression of MRP1 was sufficient to reverse the resistance of ACNU and DOX in the human glioma cell line.
Osada
Hideo
H
Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Japan.
Tokunaga
Tetsuji
T
Abe
Yoshiyuki
Y
Asai
Satomi
S
Miyachi
Hayato
H
Hatanaka
Hiroyuki
H
Tsugu
Atsushi
A
Kijima
Hiroshi
H
Yamazaki
Hitoshi
H
Shima
Katsuji
K
Ueyama
Yoshito
Y
Osamura
Yoshiyuki
Y
Nakamura
Masato
M
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015152:Blotting, Northern; D002455:Cell Division; D045744:Cell Line, Tumor; D002474:Cell-Free System; D004396:Coloring Agents / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005786:Gene Expression Regulation; D006801:Humans; D020128:Inhibitory Concentration 50; D009607:Nitrosourea Compounds / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014162:Transfection
D000903:Antibiotics, Antineoplastic; D004396:Coloring Agents; D018076:DNA, Complementary; D009607:Nitrosourea Compounds; D016337:RNA, Catalytic; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; C427204:hammerhead ribozyme; D004317:Doxorubicin; C022616:thiazolyl blue