%0 Journal Article %A TOMOYA TAKENAKA %A MIKU KATAYAMA %A AYAKA SUGIYAMA %A MASAYA HAGIWARA %A IKUO FUJII %A TOMOKA TAKATANI-NAKASE %A SUSUMU S. KOBAYASHI %A IKUHIKO NAKASE %T Gefitinib Enhances Mitochondrial Biological Functions in NSCLCs with EGFR Mutations at a High Cell Density %D 2017 %J Anticancer Research %P 4779-4788 %V 37 %N 9 %X Background/Aim: Gefitinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and has been approved for the treatment of non-small cell lung cancers (NSCLCs) with EGFR mutations. Here we demonstrated that gefitinib induced a significantly enhanced biological activity of succinate-tetrazolium reductase (STR) in mitochondria and mitochondrial membrane potential in HCC827 cells (EGFR mutation NSCLCs, sensitive to gefitinib) at a high cell density. Materials and Methods: We assessed the biological activity (STR, mitochondrial membrane potential, expression level of Bcl-2 family proteins) of gefitinib on NSCLCs at different cell densities. Results: The 3D cell culture experiments showed the enhanced mitochondrial biological activity in clustered cell culture treated with gefitinib. Interestingly, the expression levels of Bcl-xL and Bax, were affected by the cellular number and gefitinib treatment. We also found that gefitinib prevented additive anticancer activity in the combinational treatment with doxorubicin, which induces mitochondria-dependent apoptotic cell death. Conclusion: Our results indicate that gefitinib may work as a mitochondrial protector against combinational treatment with mitochondria-dependent anticancer agents in high-cell-density. %U https://ar.iiarjournals.org/content/anticanres/37/9/4779.full.pdf