[Overcoming multi-drug resistance using anti-MDR1 ribozymes].
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-tranduced 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-tranduced cells, and Rhodamine123 (Rh123) applied to test the function of Pgp.


RESULTS
The Rz-tranduced 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, China.
Chen
Xiao-ping
XP
Qiu
Fa-zu
FZ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016337:RNA, Catalytic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016337:RNA, Catalytic