人血浆样培养基微调线粒体功能并改变癌细胞系的药物敏感性

Human Plasma-Like Media fine-tune mitochondrial function and alter drug sensitivity in cancer cell lines

Keywords：Cancer cells, cell respiration, mitochondrial function, HPLM, classical media, metabolism, cell culture media, cell proliferation, cell growth, nutrients, media formulation, living cells, high-resolution respirometry, coupling control, ROUTINE respiration, LEAK respiration, electron transfer capacity, residual O2 consumption, bioenergetic cluster analysis BCA 

关键词：癌细胞、细胞呼吸、线粒体功能、HPLM、经典培养基、新陈代谢、细胞培养基、细胞增殖、细胞生长、营养物质、培养基配方、活细胞、高分辨率呼​​吸测定、耦合控制、常规呼吸、泄漏呼吸, 电子转移能力, 剩余 O2 消耗, 生物能簇分析 BCA 

生物体：人

作者：Torres-Quesada Omar, Doerrier Carolina, Strich Sophie, Gnaiger Erich, Stefan Eduard
出版期刊：《MitoFit Preprints 》（ 2022.8）

Abstract：

Two-dimensional cell cultures are established models in research for studying and perturbing cell-type specific functions. The simplicity of these models facilitates the reproducible manipulation of cultured cells. Limitations, however, relate to cell growth in a monolayer using standard cell culture media. Although such media are in use for decades, their formulations do not mimic the composition of the originating human cell environment in physiological or pathological conditions. In this study, we selected three frequently-used cancer cell lines SW620 (colon cancer), MCF7 (breast cancer), and A375 (melanoma) to determine the impact of a newly formulated human plasma-like medium (HPLM) on cell proliferation and mitochondrial function. Mitochondrial bioenergetic profiles were analyzed by high-resolution respirometry, revealing metabolic reprogramming in cells cultured in standard and HPLM media. Notably, the culturing of differentially proliferating cells in HPLM affected key mechanism of cellular respiration. All three cancer cell lines displayed an amending bioenergetic profile, particularly related to mitochondrial density and mild uncoupling of respiration. Importantly, only cells cultured in HPLM displayed mitochondrial dysfunction upon exposure with the clinically prescribed cancer drug and kinase inhibitor sunitinib. These findings highlight that cell culture media redirect mitochondrial function and affect cancer drug sensitivities. To advance the translational potential of cell culture models we propose to prioritize media with a human plasma-like composition for analyzing bioenergetic profiles and for determining target-oriented drug efficacies.

文章摘要：

二维细胞培养是研究和干扰细胞类型特定功能的研究模型。这些模型的简单性有助于培养细胞的可重复操作。然而，限制与使用标准细胞培养基在单层中的细胞生长有关。尽管这种培养基已经使用了几十年，但它们的配方并不能模拟生理或病理条件下原始人类细胞环境的组成。在这项研究中，我们选择了三种常用的癌细胞系 SW620（结肠癌）、MCF7（乳腺癌）和 A375（黑色素瘤）来确定新配制的人血浆样培养基 (HPLM) 对细胞增殖和线粒体功能。通过高分辨率呼​​吸测量法分析线粒体生物能量分布，揭示在标准和 HPLM 培养基中培养的细胞中的代谢重编程。值得注意的是，HPLM 中差异增殖细胞的培养影响了细胞呼吸的关键机制。所有三种癌细胞系都显示出一种正在改善的生物能量特征，特别是与线粒体密度和呼吸的轻度解偶联有关。重要的是，只有在 HPLM 中培养的细胞在暴露于临床处方的癌症药物和激酶抑制剂舒尼替尼后表现出线粒体功能障碍。这些发现强调了细胞培养基重定向线粒体功能并影响癌症药物敏感性。为了提高细胞培养模型的转化潜力，我们建议优先考虑具有人类血浆成分的培养基，以分析生物能量分布和确定靶向药物的功效。

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