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- 저자 : Harish C. Chandramoorthy (검색결과 1 건)
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Ayed A. Dera,Prasanna Rajagopalan,Majed Al Fayi,Irfan Ahmed,Harish C. Chandramoorthy 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.6
In this study, we report the combination ofindirubin-3-monoxime (I3M) and thymoquinone (Tq) tohave excellent therapeutic effi cacy in models of Lung cancer(LC). Preliminary screening was done with A549 cells. Cellcycle, apoptosis and NFκB phosphorylation were determinedby fl ow cytometry, while apoptotic proteins, Akt and mTORwere assessed by western blotting. Mouse xenograft modelwas used to assess the therapeutic effi cacy in-vivo . Synergisticreduction in cell viability was observed with I3M + Tqcombinations, which were non-toxic to normal HFL-1 cells. Cell cycle analysis indicated G 1 phase reduction with subsequentaccumulation of sub G 0 contents. Annexin V assayrevealed higher apoptotic cells with combinations comparedto individual treatments with a decrease in Bcl-2/Bax ratio. The combinations exhibited anti-metastasis activity in cellmigration in the scratch, scatter and tumour cell migration assays and eff ectively reduced the tumour growth in mouse xenograft model. Expression levels of p-AKT, p-mTOR,Caspase-3, p-53 and NFκB were signifi cantly reduced inthe combination treated mice compared to individual treatments. Results of current study demonstrate clear effi cacy ofI3M + Tq combinations in LC models mediated by suppressingAkt/mTOR/NFκB signalling. Further research is recommendedto transform these fi ndings into novel therapeuticcombinations against LC.
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