摘要
目的研究七氟烷在人口腔鳞状癌细胞中的抗癌作用及其潜在的分子机制。方法 MTT 比色法检测七氟烷对人口腔鳞状癌细胞的增殖抑制作用;Annexin V-FITC/PI 双染法和流式细胞术检测七氟烷对人口腔鳞状癌细胞的诱导凋亡作用、活性氧水平及加入活性氧清除剂 N-乙酰半胱氨酸(NAC)后的细胞凋亡情况;利用 Western blot 实验对凋亡相关蛋白和信号通路相关蛋白进行检测。结果 MTT 实验表明七氟烷能够抑制多种人口腔鳞状癌细胞的增殖,并且通过降低线粒体膜电位,调节人口腔鳞状癌细胞中 Bcl-2 家族、caspase-3 和 PARP 蛋白的表达,最终诱导细胞凋亡。七氟烷还促进了人口腔鳞状癌细胞中活性氧的积累,并上调 JNK、p53 蛋白的磷酸化表达水平,激活 JNK/p53 信号通路。然而,在加入 NAC 之后,不但细胞凋亡情况被抑制,JNK/p53 信号通路的激活也被显著逆转。结论七氟烷通过调节活性氧水平来激活人口腔鳞状癌细胞中的 JNK/p53 信号通路从而诱导细胞凋亡,因此七氟烷有成为治疗人口腔鳞状癌的备选药物的潜力。
Objective Sevoflurane is a commonly used anesthetic drug in clinical practice. It has a variety of pharmacological activities and can inhibit the proliferation of various cancer cells, but its effect on human oral squamous cell carcinoma is still unclear. In this study, we studied the anticancer effect of sevoflurane in human oral squamous cell carcinoma and its underlying molecular mechanism. Methods MTT colorimetric assay was used to detect the inhibitory effect of sevoflurane on human oral squamous cell carcinoma. Hochest/PI double staining and flow cytometry were used to detect the apoptosis of human oral squamous cell carcinoma cells induced by sevoflurane, the level of reactive oxygen species and apoptosis after the addition of reactive oxygen scavenger NAC. Western blot experiments were used to detect related proteins. Results Sevoflurane inhibited the proliferation of human oral squamous cell carcinoma cells and regulated the expression of Bcl-2 family, caspase-3 and PARP proteins in the cells by decreasing mitochondrial membrane potential, and eventually induced apoptosis. Sevoflurane also promoted the accumulation of ROS in human oral squamous cell carcinoma cells, up-regulated the levels of JNK and p53 phosphorylation, and activated the JNK/p53 signaling pathway. However, after the addition of the ROS scavenger NAC, not only the apoptosis was inhibited, but the activation of the JNK/p53 signaling pathway was also significantly reversed. Conclusion Sevoflurane activates JNK/p53 signaling pathway in human oral squamous cell carcinoma cells by the increment of ROS levels and the induction of apoptosis. Therefore, sevoflurane can be potentially used as a treatment for human oral squamous cell carcinoma.
作者
赵晨璐
高银亮
张国庆
ZHAO Chen-lu;GAO Yin-liang;ZHANG Guo-qing(Anesthesiology Department, Zhumadian Central Hospital, Henan 463000, China)
出处
《中国医药生物技术》
2019年第5期421-429,共9页
Chinese Medicinal Biotechnology