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Anti-MDR1 Ribozymes Mediated by Retroviral Vector Efficiently Reverse the Multidrug Resistance (MDR) in Resistant Human Lymphoma Daudi Cells
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Abstract:
In order to explore the reversal of the multidrug resistance(MDR) purely related to P-glycoprotein expression by using the anti-MDR1 ribozyme genes. Methods： Daudi human lymphoma cells 20-fold resistant to vincristine (VCR)(Daudi/MDR20) were developed. Three retroviral vectors highly expressing the anti-MDR1 ribozymes: 196MDR1-Rz, 196MDR1-sRz and iMDR1-sRz were also constructed and transfected into GP+envAM12 cells for packaging. The viral supernatants with high titers ［(1.1～2.5)×10 5 cfu/ml］ were used to infected Daudi/MDR20 cells. Results： The tRNAimet-iMDR1-sRz and tRNAimet-196MDR1-sRz-transduced Daudi/MDR20 cells effectively restored chemosensitivity to VCR and were accompanied by blocked expression of MDR1 mRNA and P-glycoprotein as well as overexpression of anti-MDR1-Rzs. Conclusion: The high level expressions of anti-MDR1 ribozymes mediated by retroviral vectors appear to have contributed to the efficinet reversal of P-gp-mediated MDR in tumor cells.
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