School of Life Sciences, Jilin University, Changchun, Jilin, 130012, China; Zhuhai Hopegenes Medical & Phamaceutical Institute, Hengqin New Area, Zhuhai, Guangdong, 519000, China.
Department of Pediatrics, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China.
Biomed Pharmacother. 2019 Oct;118:109261. doi: 10.1016/j.biopha.2019.109261. Epub 2019 Jul 30.
Doxorubicin (DOX) as a first-line chemotherapeutic drug has been widely used for therapy of human cancers. However, side effects and chemo-resistance severely blocked its clinic application. Herein, natural borneol (NB) as a novel monoterpenoid chemosensitizer was found to have the potential to increase the blood brain barrier (BBB) permeability and intracellular uptake of DOX in vitro, and synergistically enhanced DOX-induced cytotoxicity in human glioma cells. NB treatment significantly potentiated DOX-induced G2/M cell cycle arrest by triggering reactive oxygen species (ROS)-mediated DNA damage. NB also enhanced DOX-induced dysfunction of MAPKs and PI3 K/AKT pathways. Furthermore, U251 human glioma xenograft growth in vivo was also effectively inhibited by combined treatment of DOX with NB through induction of G2/M-phase arrest and antiangiogenesis. Taken together, our finding validated that NB could act as novel chemosensitizer to enhance DOX-induced anticancer efficacy, and strategy of using NB and DOX could be a high efficient way in therapy of human cancers.
阿霉素（DOX）作为一线化疗药物已广泛用于人类癌症的治疗。然而，副作用和化疗耐药性严重阻碍了其临床应用。本文中，天然龙脑（NB）作为一种新型单萜类化疗增敏剂，被发现具有增加血脑屏障（BBB）通透性和 DOX 在体外的细胞内摄取的潜力，并协同增强 DOX 诱导的人神经胶质瘤细胞的细胞毒性。NB 处理通过触发活性氧（ROS）介导的 DNA 损伤显著增强 DOX 诱导的 G2/M 细胞周期阻滞。NB 还增强了 DOX 诱导的 MAPKs 和 PI3K/AKT 通路的功能障碍。此外，通过诱导 G2/M 期阻滞和抗血管生成，NB 与 DOX 联合治疗还可有效抑制体内 U251 人神经胶质瘤异种移植物的生长。总之，我们的研究结果验证了 NB 可以作为新型化疗增敏剂增强 DOX 诱导的抗癌疗效，并且使用 NB 和 DOX 的策略可能是治疗人类癌症的一种高效方法。
