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Metabolic Signatures of Tumor Responses to Doxorubicin Elucidated by Metabolic Profiling in Ovo.
Metabolites ( IF 3.4 ) Pub Date : 2020-06-28 , DOI: 10.3390/metabo10070268
Iman W Achkar 1 , Sara Kader 1 , Shaima S Dib 1 , Kulsoom Junejo 2 , Salha Bujassoum Al-Bader 3 , Shahina Hayat 1 , Aditya M Bhagwat 4 , Xavier Rousset 5 , Yan Wang 5 , Jean Viallet 5 , Karsten Suhre 1 , Anna Halama 1
Affiliation  

Background: Dysregulated cancer metabolism is associated with acquired resistance to chemotherapeutic treatment and contributes to the activation of cancer survival mechanisms. However, which metabolic pathways are activated following treatment often remains elusive. The combination of chicken embryo tumor models (in ovo) with metabolomics phenotyping could offer a robust platform for drug testing. Here, we assess the potential of this approach in the treatment of an in ovo triple negative breast cancer with doxorubicin. Methods: MB-MDA-231 cells were grafted in ovo. The resulting tumors were then treated with doxorubicin or dimethyl sulfoxide (DMSO) for six days. Tumors were collected and analyzed using a global untargeted metabolomics and comprehensive lipidomics. Results: We observed a significant suppression of tumor growth in the doxorubicin treated group. The metabolic profiles of doxorubicin and DMSO-treated tumors were clearly separated in a principle component analysis. Inhibition of glycolysis, nucleotide synthesis, and glycerophospholipid metabolism appear to be triggered by doxorubicin treatment, which could explain the observed suppressed tumor growth. In addition, metabolic cancer survival mechanisms could be supported by an acceleration of antioxidative pathways. Conclusions: Metabolomics in combination with in ovo tumor models provide a robust platform for drug testing to reveal tumor specific treatment targets such as the antioxidative tumor capacity.

中文翻译:

卵对代谢反应的阐明对阿霉素的肿瘤反应的代谢特征。

背景:癌症代谢失调与对化学治疗的获得性耐药有关,并有助于激活癌症生存机制。然而,在治疗后激活哪些代谢途径通常仍然难以捉摸。鸡胚胎肿瘤模型(卵内)与代谢组学表型的结合可以为药物测试提供一个强大的平台。在这里,我们评估了这种方法在用阿霉素治疗卵内三阴性乳腺癌中的潜力。方法:将MB-MDA-231细胞移植到卵内。然后将产生的肿瘤用阿霉素或二甲基亚砜(DMSO)治疗六天。收集肿瘤并使用整体非靶向代谢组学和综合脂质组学进行分析。结果:我们观察到阿霉素治疗组的肿瘤生长受到明显抑制。在主成分分析中,阿霉素和DMSO治疗的肿瘤的代谢谱已明确分离。阿霉素治疗似乎触发了糖酵解,核苷酸合成和甘油磷脂代谢的抑制,这可以解释观察到的抑制的肿瘤生长。另外,抗癌途径的加速可以支持代谢癌的生存机制。结论:代谢组学与内结合 肿瘤模型为药物测试提供了一个强大的平台,以揭示肿瘤特异性治疗靶标,例如抗氧化肿瘤的能力。
更新日期:2020-06-28
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