PT - JOURNAL ARTICLE 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 TI - Gefitinib Enhances Mitochondrial Biological Functions in NSCLCs with <em>EGFR</em> Mutations at a High Cell Density DP - 2017 Sep 01 TA - Anticancer Research PG - 4779--4788 VI - 37 IP - 9 4099 - http://ar.iiarjournals.org/content/37/9/4779.short 4100 - http://ar.iiarjournals.org/content/37/9/4779.full SO - Anticancer Res2017 Sep 01; 37 AB - 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.