Hypoxia potentiates the capacity of melanoma cells to evade cisplatin and doxorubicin cytotoxicity via glycolytic shift.,FEBS Open Bio

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Hypoxia potentiates the capacity of melanoma cells to evade cisplatin and doxorubicin cytotoxicity via glycolytic shift.
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-04-14 , DOI: 10.1002/2211-5463.12830
Ming Zhuo ₁ , Falih M Gorgun ₁ , Douglas S Tyler ₁ , Ella W Englander ₁

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The hypoxic environment within solid tumors impedes the efficacy of chemotherapeutic treatments. Here, we demonstrate that hypoxia augments the capacity of melanoma cells to withstand cisplatin and doxorubicin cytotoxicity. We show that B16F10 cells derived from spontaneously formed melanoma and YUMM1.7 cells, engineered to recapitulate human‐relevant melanoma driver mutations, profoundly differ in their vulnerabilities to cisplatin and doxorubicin. The differences are manifested in magnitude of proliferative arrest and cell death rates, extent of mtDNA depletion, and impairment of mitochondrial respiration. In both models, cytotoxicity is mitigated by hypoxia, which augments glycolytic metabolism. Collectively, the findings implicate metabolic reprogramming in drug evasion and suggest that melanoma tumors with distinct genetic makeup may have differential drug vulnerabilities, highlighting the importance of precision anticancer treatments.

中文翻译：

缺氧增强了黑色素瘤细胞通过糖酵解转移逃避顺铂和阿霉素细胞毒性的能力。

实体瘤内的低氧环境阻碍了化学疗法的有效性。在这里，我们证明缺氧增加了黑色素瘤细胞抵抗顺铂和阿霉素细胞毒性的能力。我们显示，自发形成的黑色素瘤和YUMM1.7细胞衍生的B16F10细胞经过工程化，可概括人类相关的黑色素瘤驱动程序突变，其对顺铂和阿霉素的脆弱性差异很大。差异表现在增生停滞和细胞死亡率，线粒体DNA耗竭程度和线粒体呼吸功能受损等方面。在这两种模型中，缺氧可减轻细胞毒性，缺氧会增加糖酵解代谢。总的来说，

更新日期：2020-04-14

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