Maprang seed extracts suppressed chemoresistant properties of breast cancer cells survived from ionizing radiation treatment via the regulation of ABCB1 genes
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Abstract
Background: Minimal Residual Disease (MRD) is a major obstacle for eradication of cancer cells due to therapeutic resistance which results from the expression of multidrug resistant (MDR) proteins. MRD contributes to tumor metastasis and relapse in cancer patients. Therefore, any strategy that can reduce this resistance or eliminate all cancer cells must be one of the main goals for cancer treatment.
Objectives: This study aims to investigate the effect of Maprang Seed Extracts on drug resistance of minimal residual breast cancer cells that have survived radiotherapy.
Materials and methods: The treatment of resistant breast cancer cells MCF-7/IR6 and MCF-7/MPIR6 were established from parental MCF-7 cells having two different conditions for radiation treatment. Chemoresistant phenomenon of MRD was determined by MTT assay. A spectrofluorometric technique was used to determine the cellular drug uptake and the MDR protein-mediated drug efflux. MDR gene expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR).
Results: MCF-7/IR6 cells have increased resistance to doxorubicin when compared to the parental cells with the descending order of the concentration that inhibiting cell growth by 50% (IC50) as follows: MCF-7/IR6 (IC50 =342.95±30.94 nM) > MCF-7/MPIR6 (IC50 =282.75±24.64 nM) > MCF-7 (IC50 =215.42±23.73 nM), accompanied by a remarkably enhanced expression level of MDR1 genes in MCF-7/IR6 compared with parental MCF-7 cells. For the multidrug protein function, it showed that MCF-7/IR6 cells mediated higher rate of drug efflux out of cells (Va =0.2308 nM.s-1) than MCF-7/MPIR6 (Va =0.0679 nM.s-1) and the parental MCF-7 cells (Va =0.0232 nM.s-1). MPSEs effectively decreased chemoresistance phenomenon in the MCF-7/IR6 by aberrant MDR gene expression and decreased MDR protein-mediated drug efflux function.
Conclusion: The novel strategy combination of MPSEs and radiotherapy might be one strategy for improving curative effects in breast cancer treatment.
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Personal views expressed by the contributors in their articles are not necessarily those of the Journal of Associated Medical Sciences, Faculty of Associated Medical Sciences, Chiang Mai University.
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