Chemoprotection of transfer of multidrug resistance gene into human hematopoietic progenitor cell

Objective To observe the effect of the transfer of multidrug resistance gen e (mdr1) into human hematopoietic progenitor cells ( HPC) on the chemoprote ction. Methods Human CD34(+) cells served as a target of mdr1 gene transfer. Retro viral vector SF-mdr containing human total length mdr1 cDNA was introduced into packing cells GP-envAM12 by liposome-mediated transfection. The mdr1 g ene was transduced into human CD34+ cells by retroviral supernatants of pac king cells. The integration and expression of the mdr1 gene and its protein (P170) in transduced cells were determined by PCR, RT-PCR, and flow cytome try. The drug resistance of chemotherapy in transduced HPC was determined b y culturing colonies. Results The mdr1 gene was integrated and expressed in transduced CD34(+) ce lls. The efficiency of mdr1 gene transfer was 10%-14%. Compared with untran sduced controls, within a certain range of drug concentration, the number o f drug-resistant colony in transduced HPC for taxol, doxorubicin,VCR and VP 16 were increased by 3.6 +/- 2.1 fold, 2.9 +/- 0.3 fold, 1.9 +/- 0.4 fold, and 3.5 +/- 0.5 fold, respectively. Conclusion The transfer of the mdr1 gene into human HPC can increase the dr ug resistance of the transduced cells to corresponding chemotherapeutic dru gs that may provide some degree of chemoprotection for HPC.