Wang Zhihan, Ren Li, Xu Hao, Wei Zilong, Zeng Hongjun
Department of Neurosurgery, Pudong Hospital Affiliated to Fudan University, Shanghai, China.
Acta Biochim Pol. 2023 Feb 16;70(1):123-129. doi: 10.18388/abp.2020_6327.
To study the anti-proliferation activity of wilforol A against glioma cells and its possible molecular mechanisms.
Human glioma cell lines U118 MG and A172, human tracheal epithelial cells (TECs) and astrocytes (HAs) were exposed to various concentrations of wilforol A and evaluated for viability, apoptosis, and levels of proteins using WST-8 assay, flow cytometry and Western blot analysis, respectively.
Wilforol A inhibited the growth of U118 MG and A172 cells, but not TECs and HAs, in a concentration-dependent manner and the estimated IC50 were 6 to 11 μM after 4 h-exposure. Apoptosis was induced at an apoptotic rate of about 40% at 100 μM in U118 MG and A172 cells, but the rates were less than 3% in TECs and HAs. Co-exposure to caspase inhibitor Z-VAD-fmk significantly reduced wilforol A-induced apoptosis. Wilforol A treatment also reduced the colony formation ability of U118 MG cells and triggered a significant increase in ROS production. Elevated levels of pro-apoptotic proteins p53, Bax and cleaved caspase 3 and reduced level of the anti-apoptotic protein Bcl-2 were observed in glioma cells exposed to wilforol A. The expression of PI3K and p-Akt genes in the PI3K/AKT pathways were significantly downregulated in glioma cells treated with wilforol A.
Wilforol A inhibits the growth of glioma cells, reduces the levels of proteins in the P13K/Akt signal transduction pathways and increases the levels of pro-apoptotic proteins.
研究雷公藤红素A对胶质瘤细胞的抗增殖活性及其可能的分子机制。
将人胶质瘤细胞系U118 MG和A172、人气管上皮细胞（TECs）和星形胶质细胞（HAs）分别暴露于不同浓度的雷公藤红素A，并分别使用WST-8法、流式细胞术和蛋白质免疫印迹分析评估细胞活力、凋亡情况及蛋白质水平。
雷公藤红素A以浓度依赖性方式抑制U118 MG和A172细胞的生长，但对TECs和HAs无抑制作用，4小时暴露后的估计半数抑制浓度（IC50）为6至11μM。在U118 MG和A172细胞中，100μM的雷公藤红素A诱导凋亡率约为40%，但在TECs和HAs中的凋亡率低于3%。联合使用半胱天冬酶抑制剂Z-VAD-fmk可显著降低雷公藤红素A诱导的凋亡。雷公藤红素A处理还降低了U118 MG细胞的集落形成能力，并引发活性氧生成显著增加。在暴露于雷公藤红素A的胶质瘤细胞中，观察到促凋亡蛋白p53、Bax和裂解的半胱天冬酶3水平升高，抗凋亡蛋白Bcl-2水平降低。在经雷公藤红素A处理的胶质瘤细胞中，PI3K/AKT信号通路中PI3K和p-Akt基因的表达显著下调。
雷公藤红素A抑制胶质瘤细胞生长，降低PI3K/Akt信号转导通路中的蛋白质水平，并增加促凋亡蛋白水平。
