Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China.
Key Laboratory of Integrated Traditional Chinese and Western Medicine for Hematology, Health Commission of Shandong Province, Jinan 250014, China.
Biomed Pharmacother. 2023 Aug;164:114988. doi: 10.1016/j.biopha.2023.114988. Epub 2023 Jun 10.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Zinc oxide (ZnO) nanoparticles have excellent anti-tumor properties in the biomedical field. The present study aimed to explore the underlying mechanism by which ZnO nanoparticles induce toxicity in DLBCL cells (U2932) via the PINK1/Parkin-mediated mitophagy pathway. After U2932 cells were exposed to various concentrations of ZnO nanoparticles, the cell survival rate, reactive oxygen species (ROS) generation, cell cycle arrest, and changes in the expression of PINK1, Parkin, P62, and LC3 were monitored. Moreover, we investigated monodansylcadaverine (MDC) fluorescence intensity and autophagosome and further validated the results using the autophagy inhibitor 3-methyladenine (3-MA). The results showed that ZnO nanoparticles could effectively inhibit the proliferation of U2932 cells and induce cell cycle arrest at the G0/G1 phases. Moreover, ZnO nanoparticles significantly increased ROS production, MDC fluorescence intensity, autophagosome formation, and the expression of PINK1, Parkin, and LC3, and decreased the expression of P62 in U2932 cells. In contrast, the autophagy level was reduced after the intervention of the 3-MA. Overall, ZnO nanoparticles can trigger PINK1/Parkin-mediated mitophagy signaling in U2932 cells, which may be a potential therapeutic approach for DLBCL.
弥漫性大 B 细胞淋巴瘤（DLBCL）是最常见的淋巴瘤类型。氧化锌（ZnO）纳米粒子在生物医学领域具有优异的抗肿瘤特性。本研究旨在探讨 ZnO 纳米粒子通过 PINK1/Parkin 介导的线粒体自噬途径诱导 DLBCL 细胞（U2932）毒性的潜在机制。将 U2932 细胞暴露于不同浓度的 ZnO 纳米粒子后，监测细胞存活率、活性氧（ROS）生成、细胞周期停滞以及 PINK1、Parkin、P62 和 LC3 的表达变化。此外，我们研究了单丹磺酰尸胺（MDC）荧光强度和自噬体，并使用自噬抑制剂 3-甲基腺嘌呤（3-MA）进一步验证了结果。结果表明，ZnO 纳米粒子可有效抑制 U2932 细胞的增殖，并诱导细胞周期停滞在 G0/G1 期。此外，ZnO 纳米粒子显著增加了 U2932 细胞中 ROS 的产生、MDC 荧光强度、自噬体的形成以及 PINK1、Parkin 和 LC3 的表达，并降低了 P62 的表达。相反，3-MA 的干预降低了自噬水平。总之，ZnO 纳米粒子可以触发 U2932 细胞中的 PINK1/Parkin 介导的线粒体自噬信号，这可能是治疗 DLBCL 的一种潜在方法。
