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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Gefitinib Enhances Mitochondrial Biological Functions in NSCLCs with EGFR Mutations at a High Cell Density
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Gefitinib Enhances Mitochondrial Biological Functions in NSCLCs with EGFR Mutations at a High Cell Density

机译：Gefitinib在高细胞密度下增强了NSCLC中的线粒体生物功能

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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 mitochondriadependent anticancer agents in high-cell-density.
机译：背景/目的：Gefitinib是表皮生长因子受体（EGFR）的酪氨酸激酶抑制剂，并已被批准用于治疗具有EGFR突变的非小细胞肺癌（NSCLC）。在这里，我们证明，吉替尼诱导在高晶粒密度的HCC827细胞中的线粒体和线粒体膜电位中琥珀酸盐还原酶（STR）的显着增强的生物活性（EGFR突变NSCLC，对吉替尼敏感）。材料和方法：我们评估了在不同细胞密度的NSCLC上的吉替尼的生物活性（STR，线粒体膜势，BCL-2系列蛋白的表达水平）。结果：3D细胞培养实验表明，用吉非替尼处理的聚类细胞培养中增强的线粒体生物活性。有趣的是，Bcl-XL和Bax的表达水平受细胞数和吉替尼治疗的影响。我们还发现，Gefitinib预防组合治疗中的添加剂抗癌活性，其中诱导线粒体依赖性凋亡细胞死亡。结论：我们的研究结果表明，吉替尼可以作为线粒体保护器，以防止在高电池密度中用线粒体依赖性抗癌剂的组合治疗。

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