Wang Mi, Chen Bo, Chai Liang
Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Oncol Lett. 2019 Jan;17(1):1372-1378. doi: 10.3892/ol.2018.9726. Epub 2018 Nov 19.
Nasopharyngeal carcinoma (NPC) is an endothelium-associated malignancy that is heavily influenced by Epstein Barr virus infection. Triptolide, extracted from , has been proven to possess anti-inflammatory, immunosuppressive and anti-cancerous activity. Although the effect of triptolide on numerous cancer cell types has been outlined, its effect in NPC remained unclear. The present study investigated the effects and underlying mechanisms of triptolide in C666-1 and NP69 cells. It was revealed that triptolide significantly inhibited proliferation and induced apoptosis in C666-1 cells. Increased levels of cleaved-caspase-3 and apoptosis regulator BAX, decreased expression of apoptosis regulator Bcl-2, and reduced phosphorylation of RAC-α serine/threonine-protein kinase (Akt), were responsible for this induction of apoptosis. Notably, pretreating C666-1 cells with the phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002 suggested that with increasing concentrations of LY294002, triptolide exhibited decreasing ability to suppress proliferation and induce apoptosis in these cells. In conclusion, the results demonstrated that triptolide suppressed the proliferation and induced the apoptosis of C666-1 cells in a PI3K/Akt-dependent manner and therefore, may serve as a promising therapeutic candidate for NPC.
鼻咽癌（NPC）是一种与内皮相关的恶性肿瘤，受爱泼斯坦-巴尔病毒感染的影响很大。从雷公藤中提取的雷公藤内酯醇已被证明具有抗炎、免疫抑制和抗癌活性。尽管雷公藤内酯醇对多种癌细胞类型的作用已有概述，但其在鼻咽癌中的作用仍不清楚。本研究调查了雷公藤内酯醇对C666-1和NP69细胞的作用及其潜在机制。结果显示，雷公藤内酯醇显著抑制C666-1细胞的增殖并诱导其凋亡。裂解的半胱天冬酶-3和凋亡调节蛋白BAX水平升高、凋亡调节蛋白Bcl-2表达降低以及RAC-α丝氨酸/苏氨酸蛋白激酶（Akt）磷酸化减少，是这种凋亡诱导的原因。值得注意的是，用磷脂酰肌醇3激酶（PI3K）/Akt抑制剂LY294002预处理C666-1细胞表明，随着LY294002浓度的增加，雷公藤内酯醇抑制这些细胞增殖和诱导凋亡的能力下降。总之，结果表明雷公藤内酯醇以PI3K/Akt依赖的方式抑制C666-1细胞的增殖并诱导其凋亡，因此，可能是鼻咽癌的一种有前景的治疗候选药物。
