首页|PARP抑制剂Olaparib对非小细胞肺癌细胞的放疗增敏作用及其机制

PARP抑制剂Olaparib对非小细胞肺癌细胞的放疗增敏作用及其机制

扫码查看
原文链接
  • NETL
  • NSTL
  • 万方数据
目的 探讨聚腺苷二磷酸核糖聚合酶(PARP)抑制剂Olaparib对人非小细胞肺癌(NSCLC)细胞的放疗增敏作用及其可能的发生机制.方法 以人NSCLC细胞A549细胞系为研究对象,采用CCK-8实验检测不同药物浓度梯度对细胞的增殖抑制作用.选择对细胞10%抑制浓度(IC10)作为后续实验的药物浓度,实验分为对照组、Olaparib组、单纯放疗组(RT组)、Olaparib联合放疗组(Olaparib+RT组).通过克隆形成实验和EDU细胞增殖实验检测Olaparib联合放疗后的增敏效果,流式细胞术检测各组细胞周期分布,Western blot实验检测各组DNA损伤标志蛋白γ-H2AX的表达.结果 Olaparib对A549细胞具有抑制作用且呈剂量依赖性;在处理A549细胞24 h后IC10为2.593 μmol·L-1;Olaparib放疗增敏比为1.966.Olaparib+RT组A549细胞的增殖能力下降(P＜0.01);Olaparib+RT组的G2/M期细胞占比高于对照组(46.0%vs 10.8%,P＜0.05);且Olaparib+RT组细胞中γ-H2AX明显高于RT组(P＜0.01).结论 Olaparib对人NSCLC细胞A549细胞系有着放疗增敏效果,其机制可能与影响细胞周期、增加放疗后细胞DNA双链断裂形成相关.
The Radiosensitizing Effect of PARP Inhibitor Olaparib on Non-small Cell Lung Cancer Cells and Its Possible Mechanism
Objective To investigate the radiosensitizing effect of Olaparib,a poly(ADP-ribose)polymerase(PARP)inhibitor,on human non-small cell lung cancer(NSCLC)cells and its possible mechanism.Methods The A549 cell line as human NSCLC cell was used as the research object,and the CCK-8 assay was used to detect the proliferation inhibition effect of different drug concentration gradients on the cells.With the 10%inhibitory concentration(IC10)for cells established as the drug concentration,the subsequent experiments were divided into the control group,Olaparib group,radiotherapy-only group(RT group),and Olaparib combined with radiotherapy group(Olaparib+RT group).The sensitizing effect of Olaparib combined with radiotherapy was confirmed by clone formation assay and EDU cell proliferation assay;the cell cycle distribution of different treatment groups was detected by flow cytometry;the expression of the DNA damage marker protein γ-H2AX was detected by Western blot assay in each group.Results Olaparib had an inhibitory effect on A549 cells in a dose-dependent manner;the IC10 was 2.593 μmol·L-1 after Olaparib treatment of A549 cells for 24 h;the Olaparib radiosensitization ratio was 1.966;the proliferative ability of A549 cells in Olaparib+RT group was decreased(P＜0.01);the percentage of cells in G2/M phase in Olaparib+RT group was higher than that in the control group(46.0%vs 10.8%,P＜0.05);γ-H2AX in the cells of the Olaparib+RT group was significantly higher than that of the RT group(P＜0.01).Conclusion The results of this study suggest that Olaparib can produce radiosensitizing effects on A549 cells,and its mechanism may be related to the formation of cellular DNA double-strand breaks after increased radiotherapy which can affect the cell cycle.

non-small cell lung cancerpoly(ADP-ribose)polymerase inhibitorA549 cellolaparibradiosensitizationDNA damage repair

王彤、邱凌平、钱肖颖、洪卫卫、王勇、李勇

展开 >

南昌大学第一附属医院肿瘤科,南昌 330006

非小细胞肺癌 聚腺苷二磷酸核糖聚合酶抑制剂 A549肺癌细胞 奥拉帕尼 放疗增敏 DNA损伤修复

江西省自然科学基金资助项目重点项目中国抗癌协会-恒瑞PARP抑制剂肿瘤研究基金江西省中医药科技计划项目

20224ACB206026CET SDHRCORP252-3-0622022A140

2024

10.13764/j.cnki.ncdm.2024.04.004

南昌大学学报(医学版)
南昌大学

南昌大学学报(医学版)

CSTPCD
影响因子：1.008
ISSN：2095-4727
年,卷(期)：2024.64(4)