Evaluation of Combined Effect of Epigallocatechin-3-Gallate and Doxorubicin in Chemotherapy of Nsclc

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Ashwini Somayaji, Nikhat F, C S Shastry

Abstract

Background: the present study was conducted to evaluate whether the plant derived flavonoid EGCG can be an agent whose adjuvant therapy with doxorubicin possesses synergistic and chemosensitizing activity by quelling chemoresistance.The evaluation was carried out inNon small cell lung cancer cell line NCIH-460 where the cells are treated with the EGCG and doxorubicin simultaneously and sequentiallyat various combination ratios. The cell viability was analysed by SRB assay and the synergism of combination were quantitatively assessed using principle of Median effect and combination index-isobologram method using CompuSyn software. In order to understand the role of Epigallocatechin Gallate in Doxorubicin resistant cells, molecular mechanism of synergy and chemosensitization the interaction of EGCG with protein vimentin was studied using in silico method followed by western blotting in resistant cells.Results: combination treatment of Doxorubicin with the EGCG resulted in synergism when treated simultaneously. The combination ratio of 1:3(EGCG: DOXO) shows synergistic activity with up to seven fold decrease in the IC50 value of Doxorubicin. The EGCG treatment also displayed the decreased expression of vimentin in doxorubicin resistant cells that gains insight into the mechanism of synergy and chemosensitization.


Conclusions: the study demonstrated that by combining the EGCG with doxorubicin, there is a potential schedule dependent synergism and it provides a rationale for designing chemotherapeutic combination in the treatment of NSCLC.

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