文献类型：期刊文献

中文题名：PX-478通过调节HIF-1α介导的糖酵解增强肺癌放疗效果的研究

英文题名：PX-478 enhances the effect of lung cancer radiotherapy by regulating HIF-1α-mediated glycolysis

作者：杨更强[1];李洋洋[1];李启杨[1];张尚祖[1];杨玥[2];周婷[1];张利英[1,3]

第一作者：杨更强

机构：[1]甘肃中医药大学甘肃省高校重大疾病分子医学与中医药防治研究重点实验室,甘肃兰州730000;[2]西北民族大学,甘肃兰州730000;[3]甘肃中医药大学敦煌医学与转化教育部重点实验室,甘肃兰州730000

第一机构：甘肃中医药大学科研实验中心（甘肃省中医药标准化技术委员会秘书处）

年份：2025

卷号：30

期号：7

起止页码：935

中文期刊名：中国临床药理学与治疗学

外文期刊名：Chinese Journal of Clinical Pharmacology and Therapeutics

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金资助项目(82260882)。

语种：中文

中文关键词：PX-478;放疗;糖酵解;缺氧诱导因子-1α

外文关键词：PX-478;radiotherapy;glycolysis;hypoxia-inducible factor-1α

摘要：目的:研究PX-478增强肺癌放疗效果的有效性及分子机制。方法:将A549与H460细胞分为空白组、辐射组、辐射联合PX-478组。除空白组外,辐射组与PX-478组给予2Gy X射线辐照建立辐射模型,辐射联合PX-478组在造模后给予10μmol/L PX-478进行干预,培养24 h。使用倒置显微镜观察细胞生长情况及细胞数量,CCK-8法检测细胞活力,克隆形成观察细胞的增殖情况,流式细胞仪检测细胞的凋亡情况,蛋白免疫印迹法检测HIF-1α、GLUT1、HK2、PFK1、PKM2、LDHA蛋白表达情况。结果:与空白组相比,辐射组A549、H460细胞数量减少,细胞活力和增殖能力减弱,细胞凋亡率增加,HIF-1α、GLUT1、HK2、PFK1、PKM2、LDHA蛋白表达增加(P<0.01);与辐射组相比,辐射联合PX-478组H460,A549细胞数量显著减少,细胞活力和增殖能力显著减弱,细胞凋亡率显著增加,HIF-1α、GLUT1、HK2、PFK1、PKM2、LDHA蛋白表达显著降低(P<0.01)。结论:PX-478可以通过调节辐射后H460和A549细胞中HIF-1α介导的糖酵解过程,调节能量代谢,增加肿瘤细胞的凋亡,改善放疗效果。
AIM:To study the efficacy and molecular mechanism of PX-478 in enhancing radiotherapy effect of lung cancer.METHODS:H460,A549 cells were divided into blank group,radiation group and radiation combined PX-478 group.In addition to the blank group,the radiation group and the PX-478 group were given 2Gy X-ray irradiation to establish the radiation model,and the radiation combined with the PX-478 group was given 20μmol/L PX-478 intervention after modeling,and cultured for 24 h.Inverted microscope was used to observe cell growth and cell number,CCK-8 method was used to detect cell viability,cloning was used to observe cell proliferation,flow cytometry was used to detect cell apoptosis,and Western blot was used to detect HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA protein expression.RESULTS:Compared with blank group,the number of H460,A549 cells in radiation group decreased,cell viability and proliferation ability decreased,cell apoptosis rate increased,HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA protein expression increased(P<0.01).Compared with the radiation group,the number of H460,A549 cells in the radiation combined PX-478 group was significantly decreased,the cell viability and proliferation ability were significantly weakened,the apoptosis rate was significantly increased,and the protein expressions of HIF-1α,GLUT1,HK2,PFK1,PKM2 and LDHA were significantly decreased(P<0.01).CONCLUSION:PX-478 can regulate the HIF-1α-mediated glycolysis in A549,H460 cells after radiation,regulate the energy metabolism,increase the apoptosis of tumor cells,and improve the effect of radiotherapy.