Synergestic Cytotoxicity of Doxorubicin in Combination with Epigallocatechin 3-gallate in Non-Small Cell Lung Cancer by Inhibiting Protein Vimentin

Objectives

The purpose of this study was to assess the potential synergistic and chemo sensitizing effects of the plant-derived flavonoid EGCG (Epigallocatechin gallate) as an adjuvant therapy with doxorubicin in combating chemoresistance.

Materials and Methods

The evaluation was performed on the NCIH-460 non-small cell Lung cancer cell line, where the cells were treated with both EGCG and doxorubicin simultaneously and successionally at different combination ratios. The viability of the cells was anatomized using the SRB assay, and the quantitative assessment of synergism in the combinations was conducted using the Median effect principle and the combination index-isobologram method with the aid of CompuSyn software. To investigate the role of EGCG in doxorubicin-resistant cells and understand the molecular mechanisms underlying synergy and chemo sensitization, the interaction between EGCG and the protein vimentin was examined through in silico methods and confirmed by western blotting in resistant cells.

Results

The results indicated that simultaneous treatment with EGCG and doxorubicin exhibited synergistic effects, particularly at a combination ratio of 1:3 (EGCG:DOXO), which resulted in up to a seven-fold decrease in the IC5₀ value of doxorubicin. Additionally, EGCG treatment led to reduced expression of vimentin in Doxorubicin-resistant cells, shedding light on the mechanisms underlying synergy and chemo sensitization.

Conclusion

In conclusion, this study demonstrated the potential schedule-dependent synergism of combining EGCG with doxorubicin, providing a rationale for designing chemotherapeutic combinations in the treatment of Non-Small Cell Lung Cancer (NSCLC).