Department of Otolaryngology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Department of Human Anatomy Teaching and Research, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Mol Med Rep. 2018 Jun;17(6):7513-7520. doi: 10.3892/mmr.2018.8817. Epub 2018 Mar 28.
The current study aimed to identify the effect and primary mechanism of Curcumol on the migration of nasopharyngeal carcinoma (NPC) cells in vitro and in vivo. Curcumol was dissolved in absolute ethyl alcohol and the experiment was performed in NPC 5‑8F cells in vitro and in vivo. The effect of different concentrations of Curcumol on cell migration was determined using wound healing and Transwell assays. A cell counting kit‑8 (CCK‑8) assay was also performed in order to determine cell viability. Flow cytometry was used to detect the effect of Curcumol on apoptosis. The expression of epithelial‑mesenchymal transition (EMT)‑associated proteins and genes was evaluated by western blotting, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and ELISA. In addition, the antitumor activity of Curcumol was investigated in female BALB/C nude mice with orthotopic tumor implants. The results indicated that cell apoptosis was increased and the viability of NPC 5‑8F cells was decreased following treatment with Curcumol at doses of 0.1, 0.2 and 0.4 µM/ml. The results of in vivo experiments indicated that tumor growth and weight were decreased following Curcumol administration. Furthermore, the results of western blotting and RT‑qPCR demonstrated that Curcumol altered the level of E‑cadherin and N‑cadherin in a dose‑dependent manner in vivo. Curcumol also regulated the secretion of protein markers in the serum that were associated with EMT and TGF‑β1 in the 5‑8F xenograft mouse model. Thus, the results indicated that Curcumol induced TGF‑β1‑mediated EMT arrest by regulating E‑cadherin and N‑cadherin, which may prevent further development of NPC.
本研究旨在探讨莪术醇对体外和体内鼻咽癌细胞迁移的作用及其主要机制。莪术醇溶解于无水乙醇，在体外实验中采用 NPC 5-8F 细胞，在体内实验中采用 NPC 5-8F 裸鼠原位移植瘤模型进行实验。采用划痕愈合实验和 Transwell 实验检测不同浓度莪术醇对细胞迁移的影响，采用细胞计数试剂盒（CCK-8）检测细胞活力，采用流式细胞术检测莪术醇对细胞凋亡的影响。采用 Western blot、逆转录-定量聚合酶链反应（RT-qPCR）和酶联免疫吸附试验（ELISA）检测上皮间质转化（EMT）相关蛋白和基因的表达。此外，还在雌性 BALB/C 裸鼠的原位移植瘤模型中研究了莪术醇的抗肿瘤活性。结果表明，莪术醇在 0.1、0.2 和 0.4 μM/ml 剂量下能增加细胞凋亡，降低 NPC 5-8F 细胞活力。体内实验结果表明，莪术醇给药后能降低肿瘤生长和重量。此外，Western blot 和 RT-qPCR 结果表明，莪术醇能在体内以剂量依赖性方式改变 E-钙黏蛋白和 N-钙黏蛋白的水平。莪术醇还调节了与 EMT 和 TGF-β1 相关的血清蛋白标志物在 5-8F 移植瘤小鼠模型中的分泌。因此，结果表明莪术醇通过调节 E-钙黏蛋白和 N-钙黏蛋白诱导 TGF-β1 介导的 EMT 阻滞，可能阻止 NPC 的进一步发展。
