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模拟禁食饮食辅助人类荷瘤模型单一疗法的验证。

Verification of fasting-mimicking diet to assist monotherapy of human cancer-bearing models.

作者信息

Huang Wenping, Li Xiaoyang, Song Haohao, Yin Yue, Wang Hai

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Department of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

出版信息

Biochem Pharmacol. 2023 Sep;215:115699. doi: 10.1016/j.bcp.2023.115699. Epub 2023 Jul 22.

Abstract

The efficacy of a single clinical nanodrug for cancer treatment is still unsatisfactory, especially for drug-resistant cancer. Herein, we applied a fasting-mimicking diet (FMD) approach via dietary intervention to assist single clinical nanodrug for breast or ovarian cancer treatments instead of using multi-drug therapies which might cause adverse side effects. Specifically, we adopted Doxil or Abraxane to treat human breast tumor-bearing nude mice and Doxil to treat the human ovarian tumor and drug-resistant ovarian tumor-bearing nude mice under FMD conditions, respectively. According to the results, the FMD condition can promote the cellular uptake and cytotoxicity of a single nanodrug, reduce the ATP level in drug-resistant tumor cells to hinder drug efflux, normalize tumor blood vessels, relieve tumor hypoxia, and increase the accumulation of nanodrugs at tumor sites, thereby enhancing the therapeutic effects on these types of human cancers. Collectively, these results demonstrate that the FMD strategy of significance can become a practical, alternative, and promising assistant for single nanodrug for enhancing cancer therapy and clinical translation.

摘要

单一临床纳米药物用于癌症治疗的疗效仍不尽人意,尤其是对于耐药性癌症。在此,我们通过饮食干预应用禁食模拟饮食(FMD)方法来辅助单一临床纳米药物治疗乳腺癌或卵巢癌,而不是使用可能会引起不良副作用的多药疗法。具体而言,我们分别采用多柔比星脂质体(Doxil)或白蛋白结合型紫杉醇(Abraxane)治疗荷人乳腺肿瘤裸鼠,并在FMD条件下用多柔比星脂质体治疗荷人卵巢肿瘤及耐药性卵巢肿瘤裸鼠。根据结果,FMD条件可促进单一纳米药物的细胞摄取和细胞毒性,降低耐药肿瘤细胞中的ATP水平以阻碍药物外排,使肿瘤血管正常化,缓解肿瘤缺氧,并增加纳米药物在肿瘤部位的蓄积,从而增强对这些类型人类癌症的治疗效果。总体而言,这些结果表明,具有重要意义的FMD策略可成为单一纳米药物增强癌症治疗及临床转化的实用、替代性且有前景的辅助手段。

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