Overcoming multi-drug resistance by anti-MDR1 ribozyme.
OBJECTIVE
To reverse multidrug resistance (MDR) of HepG2 by anti-MDR1 hammerhead ribozyme.


METHODS
We developed an anti-MDR1 hammerhead ribozyme and delivered it to P-gp-overproducing human hepatocarcinoma cell line HepG2 by a retroviral vector containing RNA polymerase III promoter. We detected the expression of mdr1/Pgp and Rz in HepG2, HepG2 multidrug-resistant cell line and HepG2 Rz-transfected cells by real-time RT-PCR, semi-quantitative RT-PCR and Western blot methods. Moreover, MTT assay was tested to detect sensitivity of these ribozyme-transfected cells, and Rhodamine123 (Rh123) applied to test the function of Pgp.


RESULTS
The Rz- transfected HepG2 cells became doxorubicin-sensitive, concomitant with the decreases in MDR1 expression, P-gp amounts and efflux pump function.


CONCLUSIONS
The approaches using either retrovirus or liposome-mediated transfer of anti-MDR1 ribozyme may be selectively applicable to the treatment of MDR cells.
Wang
Hai
H
The Hepatic Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
Chen
Xiao-Ping
XP
Qiu
Fa-Zu
FZ
D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D019450:Genes, MDR / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D008113:Liver Neoplasms; D018613:Microscopy, Confocal; D009690:Nucleic Acid Conformation; D010641:Phenotype; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D014162:Transfection
D000970:Antineoplastic Agents; D016337:RNA, Catalytic; C427204:hammerhead ribozyme; D004317:Doxorubicin