Title:SiRNA-mediated Knockdown of ABCB1 Enhances the Efficacy of Doxorubicin and Vinorelbine in Breast Cancer Cells
Volume: 26
Issue: 5
Author(s): Zahra Abbasfard, Abbas Behzad-Behbahani*, Banafsheh Rastegari, Sirous Naeimi, Mehdi Moghanibashi and Fatemeh Safari
Affiliation:
- Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical
Sciences, Shiraz, Iran
Keywords:
Doxorubicin, drug resistance, MCF-7 cells, multiple, small interfering RNA, vinorelbine
Abstract:
Background: Breast cancer remains a leading cause of cancer-related deaths among
women, primarily attributed to the formidable challenge of multidrug resistance, often driven by
the overexpression of the ABCB1 gene.
Objective: This study aimed to assess the synergistic effects of siRNA, doxorubicin, and vinorelbine
on ABCB1 gene expression and cell viability in doxorubicin-resistant MCF-7/ADR
breast cancer cells, with siRNA targeting ABCB1 to reduce its expression and doxorubicin/ vinorelbine
to eradicate cancer cells.
Methods: Our methodology involved culturing MCF-7 and MCF-7/ADR cells in standard cell
culture conditions. The synthesized siRNA sequences transfected cells with siRNA at final concentrations
of 10, 20, and 30 nM and assessed cell viability using the MTT assay was performed.
Real-time PCR was employed to quantify ABCB1 mRNA expression levels.
Results: Results indicated that MCF-7/ADR cells exhibited substantial resistance to vinorelbine
and doxorubicin compared to MCF-7 cells, displaying resistance at 12.50 μM and 25.00 μM for
vinorelbine and 6.25 μM and 25.00 μM for doxorubicin. Remarkably, siRNA treatment effectively
reversed drug resistance in MCF-7/ADR cells across all concentrations of vinorelbine and
doxorubicin tested. When combined, siRNA, doxorubicin, and vinorelbine yielded a significantly
greater reduction in cell viability compared to individual drug treatments, particularly at a 20
μM siRNA concentration. This combination therapy also significantly suppressed ABCB1 gene
expression by a factor of 41.48 in MCF-7 cells relative to MCF-7/ADR cells.
Conclusion: these findings suggest that combining siRNA, doxorubicin, and vinorelbine holds
promise as a therapeutic strategy to overcome ABCB1-mediated multidrug resistance in breast
cancer. Further investigations and clinical trials are warranted to evaluate its clinical efficacy
rigorously.
