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首页> 外文期刊>Cell metabolism >Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance
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Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance

机译：癌症脂质代谢赋予抗炎耐药性

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摘要

Intrinsic and evasive antiangiogenic drug (AAD) resistance is frequently developed in cancer patients, and molecular mechanisms underlying AAD resistance remain largely unknown. Here we describe AAD-triggered, lipid- dependent metabolic reprogramming as an alternative mechanism of AAD resistance. Unexpectedly, tumor angiogenesis in adipose and non-adipose environments is equally sensitive to AAD treatment. AAD-treated tumors in adipose environment show accelerated growth rates in the presence of a minimal number of microvessels. Mechanistically, AAD-induced tumor hypoxia initiates the fatty acid oxidation metabolic reprogramming and increases uptake of free fatty acid (FFA) that stimulates cancer cell proliferation. Inhibition of carnitine palmitoyl transferase 1A (CPT1) significantly compromises the FFA-induced cell proliferation. Genetic and pharmacological loss of CPT1 function sensitizes AAD therapeutic efficacy and enhances its anti-tumor effects. Together, we propose an effective cancer therapy concept by combining drugs that target angiogenesis and lipid metabolism.
机译：在癌症患者中经常开发固有和稀疏的抗血管生成药物（AAD）抗性，并且由于AAD抗性的分子机制仍然很大程度上未知。在这里，我们描述了作为AAD抗性的替代机制的Aad触发的，脂质依赖性代谢重编程。出乎意料地，脂肪和非脂肪环境中的肿瘤血管生成对AAD治疗同样敏感。脂肪环境中的AAD处理的肿瘤在存在最小数量的微血管时显示出加速的生长速率。机械上，AAD诱导的肿瘤缺氧引发脂肪酸氧化代谢重编程，增加刺激刺激癌细胞增殖的游离脂肪酸（FFA）的吸收。肉毒氨基棕榈酰转移酶1a（CPT1）的抑制显着损害了FFA诱导的细胞增殖。 CPT1功能的遗传和药理学丧失敏化AAD治疗疗效，增强其抗肿瘤作用。我们共同提出了一种通过组合靶向血管生成和脂质代谢的药物来提出有效的癌症治疗概念。

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  • 来源
    《Cell metabolism》 |2018年第1期|共19页
  • 作者

    Iwamoto Hideki; Abe Mitsuhiko; Yang Yunlong; Cui Dongmei; Seki Takahiro; Nakamura Masaki; Hosaka Kayoko; Lim Sharon; Wu Jieyu; He Xingkang; Sun Xiaoting; Lu Yongtian; Zhou Qingjun; Shi Weiyun; Torimura Takuji; Nie Guohui; Li Qi; Cao Yihai;

  • 作者单位

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

    Fudan Univ Sch Basic Med Sci Dept Cellular &

    Genet Med Shanghai 200032 Peoples R China;

    Sun Yat Sen Univ State Key Lab Ophthalmol Zhongshan Ophthalm Ctr Guangzhou Guangdong Peoples R;

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

    Shenzhen Univ Affiliated Hosp 1 Peoples Hosp Shenzhen 2 Key Lab Int Collaborat Shenzhen 518035;

    Shandong Acad Med Sci Shandong Eye Inst Shandong Prov Key Lab Ophthalmol State Key Lab Cultivat;

    Shandong Acad Med Sci Shandong Eye Inst Shandong Prov Key Lab Ophthalmol State Key Lab Cultivat;

    Kurume Univ Sch Med Dept Med Div Gastroenterol Kurume Fukuoka Japan;

    Shenzhen Univ Affiliated Hosp 1 Peoples Hosp Shenzhen 2 Key Lab Int Collaborat Shenzhen 518035;

    Shanghai Univ Tradit Chinese Med Shuguang Hosp Dept Med Oncol Shanghai Peoples R China;

    Karolinska Inst Dept Microbiol Tumor &

    Cell Biol S-17177 Stockholm Sweden;

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  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
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