TY - JOUR T1 - Gefitinib Enhances Mitochondrial Biological Functions in NSCLCs with <em>EGFR</em> Mutations at a High Cell Density JF - Anticancer Research JO - Anticancer Res SP - 4779 LP - 4788 VL - 37 IS - 9 AU - TOMOYA TAKENAKA AU - MIKU KATAYAMA AU - AYAKA SUGIYAMA AU - MASAYA HAGIWARA AU - IKUO FUJII AU - TOMOKA TAKATANI-NAKASE AU - SUSUMU S. KOBAYASHI AU - IKUHIKO NAKASE Y1 - 2017/09/01 UR - http://ar.iiarjournals.org/content/37/9/4779.abstract N2 - 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. ER -