4.8 Article

Dose-Dependent Carbon-Dot-Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism

期刊

ADVANCED SCIENCE
卷 8, 期 8, 页码 -

出版社

WILEY
DOI: 10.1002/advs.202002404

关键词

glutamine; metabolomics; mTOR; ROS; uveal melanoma

资金

  1. National Natural Science Foundation of China [81972530, U1932135, 81601623]
  2. National Key R&D Program of China [2018YFC1106100, 2018YFC1106101]
  3. Shanghai Rising-Star Program [17QA1402000]
  4. Fund for Excellent Young Scholars of Shanghai Ninth People's Hospital
  5. Shanghai Jiao Tong University School of Medicine [JYYQ001]
  6. China Scholarship Council [201906235030]
  7. Shanghai Science and Technology Committee [17DZ2260100]

向作者/读者索取更多资源

This study investigates the effects of carbon dots on uveal melanoma cell metabolomics, growth, invasiveness, and tumorigenicity, demonstrating that moderate doses of carbon dots can promote tumorigenicity in cancer cells.
Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized. Here, the effects of Cdots on UM cell metabolomics, growth, invasiveness, and tumorigenicity are investigated in vitro and in vivo zebrafish and nude mouse xenograft model. Cdots dose-dependently increase ROS levels in UM cells. At Cdots concentrations below 100 mu g mL(-1), Cdot-induced ROS promote UM cell growth, invasiveness, and tumorigenicity; at 200 mu g mL(-1), UM cells undergo apoptosis. The addition of antioxidants reverses the protumorigenic effects of Cdots. Cdots at 25-100 mu g mL(-1) activate Akt/mammalian target of rapamycin (mTOR) signaling and enhance glutamine metabolism, generating a cascade that promotes UM cell growth. These results demonstrate that moderate, subapoptotic doses of Cdots can promote UM cell tumorigenicity. This study lays the foundation for the rational application of ROS-producing nanoparticles in tumor imaging and therapy.

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