RT Journal Article SR Electronic T1 Anti-MDR1 siRNA Restores Chemosensitivity in Chemoresistant Breast Carcinoma and Osteosarcoma Cell Lines JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2813 OP 2820 VO 31 IS 9 A1 JENNIFER PEREZ A1 CHRISTINE BARDIN A1 CHANTAL RIGAL A1 BESSE ANTHONY A1 RAPHAËL ROUSSEAU A1 AURELIE DUTOUR YR 2011 UL http://ar.iiarjournals.org/content/31/9/2813.abstract AB Background: Reversion of chemoresistance by inhibition of P-glycoprotein (P-gp) expression may overcome the chemoresistance observed in many cancer types and may allow for improved therapeutic ratio. We investigated whether siRNA specific for ABCB1 (MDR1) mRNA might restore sensitivity to chemotherapy in tumor cell lines known to overexpress the MDR1 gene. Materials and Methods: MDR1-expressing tumor cell lines were transiently transfected with anti-MDR1 silencing RNA (siRNA) before exposure to doxorubicin or methotrexate. The capacity of siRNA to reduce cell proliferation and increase the IC50 of the tested chemotherapies was investigated. Results: siRNA down-regulated MDR1 mRNA expression by 50% in breast carcinoma and osteosarcoma cell lines, and significantly inhibited tumor cell proliferation up to 90% (p<0.01), when co-administered with doxorubicin or methotrexate, despite the known chemoresistance of the cell lines. siRNAs reduced the IC50 of doxorubicin and methotrexate by more than 10-fold (p<0.01). Conclusion:These results suggest the potential clinical application of anti-MDR1 siRNA to restore chemosensitivity and possibly improve the therapeutic ratio of these cytotoxic drugs.