Objective: To investigate the effect of mdr1 antisense oligodeoxynucleotides (ASON) on reversal of multidrug resistance in ovarian carcinoma cells.
Methods: Drug resistance ovarian carcinoma cells SKOV3/mdr1 transducted with human multidrug resistance gene (mdr1) were served as models. The positive rate and function of the mdr1 gene product P-glycoprotein (P-gp) in SKOV3/mdr1 cells after mdr1-ASON (250 micrograms/ml) treatment were determined by flow cytometry and rhodamine 123 efflux trial. Drug resistance of SKOV3/mdr1 cells was also observed by cell colony culture.
Results: P-gp positive rate of SKOV3/mdr1 cells after mdr1-ASON treatment was decreased from 38.9% to 21.3% (P < 0.01). Intracellular rhodamine retension in SKOV3/mdr1 cells after mdr1-ASON treatment was increased from 32.1% to 50.7% (P < 0.01). Under effect of Taxol 5 ng/ml, the relative percents of drug-resistant colony in mdr1-ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 8% and 63%, respectively, (P < 0.01). Under effect of Doxorubicin 100 ng/ml, the relative percents of drug-resistant colony in mdr1-ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 34% and 79%, respectively, (P < 0.01).
Conclusion: mdr1-ASON can reverse multidrug resistance of ovarian carcinoma cell in a certain extent so as to increase chemotherapeutic sensitivity of ovarian carcinoma cells.