Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; Department of Holistic Wellness, Mingdao University, Changhua 52345, Taiwan.
Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan.
Phytomedicine. 2019 May;58:152805. doi: 10.1016/j.phymed.2018.12.028. Epub 2018 Dec 24.
Developing resistance to chemotherapeutic drugs has become a major problem in the management of nasopharyngeal carcinoma (NPC). To overcome this issue, use of natural plant products as chemosensitizers is gaining importance at a fast pace.
HYPOTHESIS/PURPOSE: The present study was designed to evaluate the cytotoxic effect and mode of action of a natural pentacyclic triterpenoid, celastrol, on cisplatin-resistant NPC cells.
Study results revealed that celastrol treatment significantly reduced the viability of NPC cells in dose and time dependent manners, as compared to untreated control cells. The cytotoxic effect of celastrol was mediated by cell cycle arrest at G2/M phase and induction of intrinsic and extrinsic apoptotic pathways. With further analysis, we observed that celastrol-induced activation of caspases was accompanied by increased phosphorylation of MAPK pathway proteins, p38, ERK1/2.
Taken together, our observation provides a novel insight on use of a natural plant product, celastrol, in the management of chemoresistant NPC.
化疗药物耐药性的产生已成为鼻咽癌（NPC）治疗的主要问题。为了克服这一问题，天然植物产品作为化疗增敏剂的应用正迅速受到重视。
假说/目的：本研究旨在评估天然五环三萜化合物雷公藤红素对顺铂耐药 NPC 细胞的细胞毒性作用及其作用机制。
研究结果表明，与未处理的对照组细胞相比，雷公藤红素处理以剂量和时间依赖的方式显著降低 NPC 细胞的活力。雷公藤红素的细胞毒性作用是通过细胞周期阻滞在 G2/M 期和诱导内在和外在凋亡途径介导的。进一步分析表明，我们观察到雷公藤红素诱导的半胱天冬酶激活伴随着 MAPK 通路蛋白 p38、ERK1/2 的磷酸化增加。
综上所述，我们的观察结果为天然植物产物雷公藤红素在耐药性 NPC 的治疗中的应用提供了新的见解。
