热疗靶向降解p38γ抑制鼻咽癌细胞增殖  

Targeted degradation of p38γby hyperthermia inhibits proliferation of nasopharyngeal carcinoma cells

作　　者：吴晶晶 李慧珍[2] 石淑玲 李培鸿 杨玉川 查博娅 皇甫林宽 梁天嵩 郑颖娟 杨道科 WU Jingjing;LI Huizhen;SHI Shuling;LI Peihong;YANG Yuchuan;ZHA Boya;HUANGFU Linkuan;LIANG Tiansong;ZHENG Yingjuan;YANG Daoke(School of Basic Medicine,Zhengzhou University,Henan Zhengzhou 450000,China;Radiotherapy Department,the First Affiliated Hospital of Zhengzhou University,Henan Zhengzhou 450000,China)

机构地区：[1]郑州大学基础医学院,河南郑州450000 [2]郑州大学第一附属医院放疗科,河南郑州450000

出　　处：《现代肿瘤医学》2024年第24期4588-4599,共12页Journal of Modern Oncology

基　　金：河南省卫生健康委员会项目(编号:LHGJ20220371)。

摘　　要：目的:研究热疗对鼻咽癌细胞增殖的影响及其作用机制。方法:采用水浴法模拟热疗。采用CCK-8、EdU核染色和克隆形成实验分析鼻咽癌细胞系CNE-2经43℃热疗处理后以及p38γ基因敲除和过表达的增殖情况。流式细胞术检测细胞周期参数和凋亡,qPCR和Western blot检测p38γmRNA和蛋白表达水平。Transwell法和划痕法检测细胞迁移。结果:与p38γ基因下调类似,热疗处理后的鼻咽癌细胞表现出与p38γ靶基因下调相关的生长抑制,并且发现高温也阻断了细胞周期。然而,高温治疗后,p38γ过表达细胞的增殖受到抑制。此外,高温增加了p38γ的溶酶体的破坏,导致鼻咽癌中p38γ蛋白水平下降。生物信息学分析表明,p38γ的下调是鼻咽癌细胞热反应的中心节点。结论:我们的研究表明,高温可以很容易地破坏鼻咽癌细胞中的p38γ分子水平,抑制肿瘤生长,有效地阻断细胞周期。因此,热疗在治疗p38γ驱动的癌症中提供了一种提高治疗效果的新策略。Objective:To investigate the effect of hyperthermia(HT)on nasopharyngeal carcinoma(NPC)cells proliferation and its mechanism.Methods:Water bath method was used to simulate HT.The proliferation of NPC cell line CNE-2 after 43℃HT,p38γ gene knockout and overexpression were analyzed by CCK-8,EdU nuclear staining and clonal formation assay.Cell cycle parameters and apoptosis were detected by flow cytometry,p38γmRNA and protein expression levels were detected by qPCR and Western blot.Cell migration was detected by Transwell and scratch methods.Results:Similar to the downregulation of the p38γgene,high-temperature treated NPC cells showed growth inhibition associated with downregulation of p38γ.And high temperatures were also found to block the cell cycle.However,the proliferation of cells with p38γoverexpression was inhibited after HT treatment.Furthermore,high temperature increased the destruction of p38γ-lysosome,leading to a decrease in the level of p38γprotein in NPC.Bioinformatics analysis showed that down-regulation of p38γ was the central node of the thermal response of NPC cells.Conclusion:High temperatures can easily disrupt the level of p38γNPC cells and inhibit tumor growth,effectively blocking the cycle.Therefore,hyperthermia is a new strategy to improve the therapeutic effectiveness of p38γ-driven cancers.

关 键 词：p38γ 鼻咽癌 热疗 增殖 

分 类 号：R739.63[医药卫生—肿瘤]