scholarly journals Clinical effect of astragaloside IV on breast carcinoma cells based on MDR1: A randomised trial

2021 ◽  
Vol 20 (11) ◽  
pp. 2311-2316
Author(s):  
Liangdong Chen ◽  
Deqiang Zhuo ◽  
Hongyin Yuan

Purpose: To study the clinical effect of astragaloside IV on breast carcinoma cells (BCCs), and its potential mechanisms with respect to multiple drug resistance-1 (MDR1)Methods: The cytotoxicity of astragaloside IV to BCCs was determined using CCK-8 test, and values of its half inhibitory concentration (IC50) were determined. Transwell assay and flow cytometry were performed to determine the effect of astragaloside (13 μg/mL) on cell invasion and apoptosis. The contents of MDR1 mRNA in BC tissues and cells were determined using real-time quantitative polymerase chain reaction (qRT-PCR), while the protein expression levels of MDR1 in BC cells were determined using western blot assay.Results: The IC50 of astragaloside IV for MCF-7 and MDA-MB-231 BCCs were 12.57 μg/mL and 13.91 μg/mL, respectively. Transwell experiment showed significantly inhibited invasive capacity and enhanced apoptotic potential of the BCCs after astragaloside IV intervention. However, invasive capacities of the BCCs were markedly enhanced, while their apoptotic capacities were inhibited after transfection with si-MDR1, when compared with controls (p < 0.05). Results of qRT-PCR revealed that the mRNA content of MDR1 in BC tissues and cells (0.42±0.11) was significantly lower than that in normal tissues (0.95±0.18; p < 0.05). Results from western blot assay revealed that the relative expression levels of MDR1 protein were decreased, with values of 0.21±0.05, 0.32±0.07 and 0.74±0.15 for MCF-10A, MCF-7, MAD-MB-231 and MCF-10A, respectively (p < 0.05).Conclusion: Astragaloside IV regulates the metastasis and apoptosis of BCCs through regulation of MDR1. It also inhibits cell invasion but enhances the apoptosis of BC cells transfected with si-MDR1. These results highlight the prospects of the compound for the treatment of BC.

ChemInform ◽  
2010 ◽  
Vol 32 (35) ◽  
pp. no-no ◽  
Author(s):  
Yves Jacquot ◽  
Laurent Bermont ◽  
Herve Giorgi ◽  
Bernard Refouvelet ◽  
Gerard L. Adessi ◽  
...  

2016 ◽  
Vol 38 (4) ◽  
pp. 1643-1651 ◽  
Author(s):  
Jing Yan ◽  
Bingbing Zhang ◽  
Zohreh Hosseinzadeh ◽  
Florian Lang

Background/Aims: Oscillations of cytosolic Ca2+ activity ([Ca2+]i) participate in the orchestration of tumor cell proliferation. [Ca2+]i could be increased by intracellular Ca2+ release followed by store-operated Ca2+-entry (SOCE). [Ca2+]i could be decreased by Ca2+ extrusion via Na+/Ca2+ exchange. Mechanisms accomplishing SOCE include the pore-forming ion channel unit Orai1 and its regulator STIM1, Na+/Ca2+ exchanger isoforms include NCX1. In MCF-7 breast carcinoma cells Orai1 and NCX1 have previously been shown to be modified by pharmacological inhibition of Janus activated kinase JAK2. The present study explored whether SOCE and Na+/Ca2+ exchange are similarly sensitive to pharmacological JAK3 inhibition. Methods: MCF-7 breast carcinoma cells were studied in the absence and presence of the JAK3 inhibitor WHI-P154 (22 µM). [Ca2+]i was estimated from Fura-2-fluorescence, SOCE from increase of [Ca2+]i following Ca2+ re-addition after Ca2+-store depletion with sarcoendoplasmatic Ca2+-ATPase (SERCA) inhibitor thapsigargin (1 µM), and Na+/Ca2+ exchanger activity from increase of [Ca2+]i following extracellular Na+ removal. Transcript levels were quantified with RT-PCR. Results: Addition of ATP (100 µM) was followed by a rapid increase of [Ca2+]i, which was significantly blunted by WHI-P154. Thapsigargin-induced intracellular Ca2+ release was not appreciably influenced by WHI-P154. Subsequent SOCE was, however, significantly blunted by WHI-P154. WHI-P154 further significantly decreased Orai1 transcript levels. The increase of [Ca2+]i following extracellular Na+-removal and the NCX1 transcript levels were similarly decreased by WHI-P154. Conclusions: The JAK3 inhibitor WHI-P154 decreases both, Orai1 and NCX1 transcript levels and thus impairs SOCE and Na+/Ca2+ exchange.


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