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Updated: Aug 18, 2026

Bacterial Delivery of RNAi Effectors: Transkingdom RNAi
Published on: August 18, 2010
Modulation of BCRP mediated atypical multidrug resistance phenotype by RNA interference
1Department of Pathology, Medical School, Shandong University, Jinan, 250012 Shandong Province, P.R.China.
Abstract:
Multidrug resistance (MDR) in human cancers is one of the major causes of failure of chemotherapy. The emergence of breast cancer resistance protein (BCRP), a member of the ABC transporter family, has necessitated the development of antagonists. To overcome the BCRP-mediated atypical multidrug drug resistance, two small interfering RNA constructs (RNAi) targeting two different regions of BCRP mRNA were designed to inhibit the atypical MDR expression by transfecting them into MCF-7/MX100 cell lines. The multidrug resistance index to mitoxantrone and the intensity of mitoxantrone fluorescence of MCF-7/MX100 decreased after transfected by pSUPER-BCRP-A and pSUPER-BCRP-B respectively; the BCRP mRNA level and the BCRP protein level of MCF-7/MX100 decreased after treated with pSUPER-BCRPs. The two constructed RNAi plasmids could reverse the atypical mutidrug resistance mediated by BCRP, but neither can reversed it completely, this may be due to low transfection efficiency and transient transfection.
Insights
Small interfering RNA (siRNA) targeting breast cancer resistance protein (BCRP) reduced multidrug resistance in cancer cells. While effective, complete reversal was limited by transfection efficiency.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) in human cancers significantly hinders chemotherapy efficacy.
- Breast cancer resistance protein (BCRP), an ABC transporter, is implicated in atypical MDR.
- Developing BCRP antagonists is crucial for overcoming treatment failures.
Purpose of the Study:
- To investigate the potential of small interfering RNA (siRNA) to inhibit BCRP-mediated MDR.
- To design and evaluate two siRNA constructs targeting different regions of BCRP mRNA.
Main Methods:
- Two siRNA constructs (pSUPER-BCRP-A and pSUPER-BCRP-B) were designed to target BCRP mRNA.
- These constructs were transfected into MCF-7/MX100 cell lines to assess their impact on BCRP expression and function.
- Mitoxantrone resistance index and fluorescence intensity were measured to evaluate MDR reversal.
Main Results:
- Transfection with pSUPER-BCRP-A and pSUPER-BCRP-B led to decreased mitoxantrone resistance and fluorescence intensity in MCF-7/MX100 cells.
- Both BCRP mRNA and protein levels were reduced following treatment with the siRNA constructs.
- The siRNA plasmids demonstrated the ability to reverse BCRP-mediated atypical MDR.
Conclusions:
- siRNA constructs targeting BCRP can effectively reverse atypical multidrug resistance in cancer cells.
- Complete reversal of MDR was not achieved, potentially due to limitations in transfection efficiency and transient expression.
- Further optimization of siRNA delivery and stability is warranted for enhanced therapeutic outcomes.
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