Abstract:
Objective
To study the effect of small interfering RNAs（siRNAs）combined with antisense oligodeoxyribonucleotides（asODNs），which targeted MDR1 gene，on reversing multidrug resistance of human breast cancer cell line MCF-7/ADR.
Methods
The siRNAs and asODNs which targeted the same sequences of MDR1 gene were designed and synthesized.Human breast cancer MCF-7/ADR cells were cultured and tranfected with asODNs，siRNAs＋asODNs，siRNAs，and negative siRNAs using lipofectamineTM 2000，respectively.MDR-1mRNA was assayed by RT-PCR and the protein expression was detected by Western blotting.The function of P-glycoprotein（P-gp）was detected by rhodamine 123 retention and the resistant efficiency of MCF-7/ADR to ADM was determined by MTT method.
Results
The expressions of MDR-1mRNA and protein decreased significantly after transfection of asODNs，siRNAs＋asODNs，and siRNAs respectively.The transporting function of P-gp increased and the resistance of MCF-7/ADR to ADM reversed significantly.The reversing effect increased significantly by siRNAs combined with asODNs.The inhibition effect of the siRNAs with lower concentration（200 nmol/L）was greater than that of asODNs with higher concentration（5μmol/L）.
Conclusion
siRNAs and asODNs could reverse multidrug resistance of human breast cancer cell line MCF-7/ADR.The inhibition effect is increased significantly by siRNAs combined with asODNs.
Key words:
SiRNAs,
Antisense oligodeoxyribonucleotides,
Gene,
MDR-1,
Drug resistance,
Neoplasm
Jun-min WEI, Ming HOU, Li-zhen LI, Peng GAO. Reversal of multidrug resistance of human breast cancer MCF-7/ADR cells by small interfering RNAs combined with antisense oligodeoxyribonucleotides for inhibition of MDR1 gene expression[J]. Chinese Journal of Breast Disease(Electronic Edition), 2008, 02(04): 436-442.