MTH1抑制剂TH287用于口腔癌治疗的疗效及机制研究  

MTH1 Inhibitor(TH287)for the Treatment of Oral Cancer Research on Therapeutic Efficacy and Mechanism

作　　者：石晓蕾 安云杰 褚彩娟 SHI Xiaolei;AN Yunjie;CHU Caijuan(Dental Department,Weifang Yidu Central Hospital,Qingzhou City,Shandong Province 262500;不详)

机构地区：[1]潍坊益都中心医院口腔科,山东省青州市262500 [2]青州市人民医院麻醉科 [3]潍坊益都中心医院手术室

出　　处：《医学理论与实践》2025年第5期729-734,共6页The Journal of Medical Theory and Practice

摘　　要：目的:探讨MTH1(MutT同源蛋白1)抑制剂TH287对口腔癌细胞CAL27增殖、迁移、侵袭及凋亡的影响,并揭示其潜在的作用机制。方法:采用人口腔癌细胞CAL27细胞,通过CCK-8、克隆形成、划痕、Transwell实验评估TH287对增殖迁移的影响;Annexin V-FITC/PI及线粒体膜电位检测分析凋亡效应;Western blot检测凋亡蛋白及PI3K/AKT通路变化;SC79预处理验证TH287经PI3K/AKT通路调控凋亡。结果:TH287能够显著抑制CAL27细胞的增殖和迁移能力。CCK-8实验和克隆形成实验结果显示,随着TH287浓度的增加,CAL27细胞的增殖活力逐渐降低,集落形成数量显著减少。划痕试验和Transwell实验进一步佐证该抑制剂对细胞的抑制作用。Annexin V-FITC/PI双染实验显示TH287显著诱导CAL27细胞凋亡,表现为凋亡细胞比例的增加;线粒体膜电位检测发现在TH287处理下,CAL27细胞的线粒体膜电位明显降低。Western blot分析表明,TH287浓度与抗凋亡蛋白Bcl-2的表达水平、Bcl-2/Bax比值成反比,与促凋亡蛋白Bax的表达水平成正比。此外,TH287能够抑制PI3K/AKT信号通路的活化,降低AKT的磷酸化水平。进一步使用AKT磷酸化激活剂SC79进行预处理显示,细胞活力增加和凋亡率降低,说明PI3K/AKT信号通路可能与TH287调控CAL27细胞的凋亡有关。结论:MTH1抑制剂TH287对口腔癌细胞CAL27具有显著的抗肿瘤作用,其作用机制可能与抑制PI3K/AKT信号通路、诱导细胞凋亡有关。Objective:Explore the effects of TH287,an MTH1(MutT Homolog 1)inhibitor,on the proliferation,migration,invasion,and apoptosis of oral cancer cells CAL27,and elucidate its underlying mechanisms.Methods:Using human oral cancer CAL27 cells,the effects of TH287 on proliferation and migration were assessed through CCK-8,clone formation,scratch,and Transwell experiments.Apoptotic effects were analyzed by Annexin V-FITC/PI and mitochondrial membrane potential measurements.Western blot was employed to detect changes in apoptotic proteins and the PI3K/AKT pathway.Pretreatment with SC79 was used to verify that TH287 regulates apoptosis via the PI3K/AKT pathway.Results:TH287 significantly inhibits the proliferation and migration abilities of CAL27 cells.The results of the CCK-8 and clone formation experiments demonstrate that as the concentration of TH287 increases,the proliferative activity of CAL27 cells gradually decreases,and the number of colonies formed significantly reduces.The wound healing(scratch)and Transwell experiments further corroborate the inhibitory effects of this inhibitor on the cells.The Annexin V-FITC/PI double staining experiment shows that TH287 notably induces apoptosis in CAL27 cells,manifested by an increase in the proportion of apoptotic cells;mitochondrial membrane potential measurements reveal that under TH287 treatment,the mitochondrial membrane potential of CAL27 cells is significantly reduced.Western blot analysis indicates that the concentration of TH287 is inversely proportional to the expression level of the anti-apoptotic protein Bcl-2 and the Bcl-2/Bax ratio,while it is directly proportional to the expression level of the pro-apoptotic protein Bax.Furthermore,TH287 can inhibit the activation of the PI3K/AKT signaling pathway,reducing the phosphorylation level of AKT.Additional pretreatment with the AKT phosphorylation activator SC79 shows increased cell viability and decreased apoptosis rate,suggesting that the PI3K/AKT signaling pathway may be involved in the regulation of CAL27 cell a

关 键 词：口腔癌 细胞凋亡 MTH1抑制剂 TH287 

分 类 号：R739.8[医药卫生—肿瘤]