OBJECTIVETo reverse multidrug resistance (MDR) of HepG2 by anti-MDR1 hammerhead ribozyme.

METHODSWe 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.

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

CONCLUSIONSThe approaches using either retrovirus or liposome-mediated transfer of anti-MDR1 ribozyme may be selectively applicable to the treatment of MDR cells.