PARP-1抑制剂Olaparib对MCF-7乳腺癌的放疗增敏作用及乏氧显像  

Radiosensitizing effect of PARP-1 inhibitor Olaparib on MCF-7 breast cancer and hypoxic imaging

作　　者：许阿磊 薛杨央[1] 陶伟涛 王思淇 金娟[2] 徐慧琴[1] XU A-lei;XUE Yang-yang;TAO Wei-tao;WANG Si-qi;JIN Juan;XU Hui-qin(Dept of Nuclear Medicine,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;School of Basic Medical Sciences,Anhui Medical University,Hefei 230032,China)

机构地区：[1]安徽医科大学第一附属医院核医学科,安徽合肥230022 [2]安徽医科大学基础医学院,安徽合肥230032

出　　处：《中国药理学通报》2023年第9期1668-1674,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81971643)。

摘　　要：目的探讨PARP抑制剂Olaparib对MCF-7乳腺癌模型的放疗增敏作用,并通过^(18)F-氟赤式硝基咪唑(^(18)F-FETNIM)PET/CT监测Olaparib的放疗增敏效应。方法建立MCF-7乳腺癌模型,按随机数字表法分为对照组、Olaparib组、放疗(IR)组、Olaparib+IR组;定期测量肿瘤大小,并统计荷瘤鼠生存时间;治疗前后进行^(18)F-FETNIM PET/CT显像,定量分析肿瘤/肌肉比值(TMR)。对HIF-1α、Ki67及p53蛋白进行免疫组织化学分析;分析TMR与HIF-1α、Ki67及p53的相关性。数据分析采用配对t检验、两独立样本t检验、单因素方差分析和Pearson相关分析。结果Olaparib单独应用时对肿瘤疗效甚微,当与放疗联合时,可减缓肿瘤生长速度,延长生存周期;治疗前,各组之间的TMR值差异无统计学意义;治疗后,与IR组相比,Olaparib+IR组的TMR值明显降低,差异有统计学意义;免疫组化结果显示,与IR组相比,HIF-1α、Ki67及p53在Olaparib+IR组中表达最低(P=0.004;P=0.002;P<0.001);TMR与HIF-1α、Ki67及p53呈正相关性(r=0.918;r=0.919;r=0.914)。结论Olaparib联合放疗能够抑制肿瘤生长,延长生存周期,下调HIF-1α、Ki67及p53等生物标志物,对MCF-7乳腺癌具有放疗增敏作用,同时,^(18)F-FETNIM PET/CT显像能够动态监测肿瘤乏氧情况,反映放疗增敏疗效。Aim To investigate the radiosensitizing effect of the PARP inhibitor Olaparib on MCF-7 breast cancer model and to monitor the radiosensitizing effect of Olaparib by ^(18)F-Fluoroerythronitroimidazole(^(18)F-FETNIM)PET/CT.Methods MCF-7 breast cancer model was established and divided into control group,Olaparib group,irradiation group and Olaparib+irradiation group according to random number table method;tumor volume was measured to calculate tumor inhibition rate and survival time of tumor-bearing mice was counted.^(18)F-FETNIM PET imaging was performed before and after treatment,and the tumor/muscle ratio(TMR)was calculated for quantitative analysis.Immunohistochemical staining was used to analyze the changes in the expression of HIF-1α,Ki67 and p53 proteins;The correlations between TMR and the expression of HIF-1α,Ki67 and p53 were analyzed.Data were analyzed by paired t-test,two independent samples t-test,one-way ANOVA,and Pearson correlation analysis.Results Olaparib alone had little effect on the tumor,but when combined with irradiation,the tumor growth rate was significantly slower and the survival period was significantly prolonged;PET/CT results showed that the differences in tumor TMR values between the control group,Olaparib group,IR group and Olaparib+IR group before treatment were not statistically significant(F=0.24,P>0.050);after treatment,the tumor TMR values in the IR group and Olaparib+IR group were reduced to different degrees,and the decrease was more significant in the combined group,and the difference between the two groups was statistically(P<0.039).Immunohistochemical results showed that HIF-1α,Ki67 and p53 proteins were the least expressed in the combined group compared to the IR group(P=0.004;P=0.002;P<0.001).TMR was significantly and positively correlated with the expression of HIF-1α,Ki67,and p53(r=0.918;r=0.919;r=0.914).Conclusions Olaparib suppresses tumor volume,prolongs the survival cycle of tumor-bearing mice,and downregulates several biomarkers associated with poor prognosis in

关 键 词：MCF-7 PARP抑制剂 放射治疗 放疗敏感性 肿瘤乏氧 ^(18)F-FETNIM 

分 类 号：R-332[医药卫生] R737.905R815R979.1