光敏剂5-氨基酮戊酸联合阿霉素对乳腺癌荷瘤裸鼠光动力作用及其机制的研究  

Photodynamic effect of photosensitizer 5-aminolevulinic acid combined with doxorubicin on nude mice bearing breast cancer and its mechanism

作　　者：祝寅[1] 陈苏杰 Zhu Yin;Chen Sujie(Department of Hematology and Oncology,The People's Hospital of Jurong,Jurong 212400,China;Department of CT,The People's Hospital of Jurong,Jurong 212400,China)

机构地区：[1]江苏省句容市人民医院血液肿瘤科,212400 [2]江苏省句容市人民医院CT室,212400

出　　处：《国际医药卫生导报》2021年第17期2679-2682,共4页International Medicine and Health Guidance News

基　　金：句容市民生科技计划项目(SF2019215035)。

摘　　要：目的采用随机对照实验探讨光敏剂5-氨基酮戊酸(5-ALA)联合阿霉素(DOX)治疗乳腺癌的作用及其可能机制。方法2020年10月采用4T1小鼠乳腺癌细胞和BALB/c-nu/nu裸鼠建立乳腺癌荷瘤裸鼠模型,将32只荷瘤裸鼠分为4组(每组8只):空白对照组(不给任何治疗)、DOX组(2 mg/kg DOX)、光动力治疗(PDT)组(50 mg/kg 5-ALA+660 nm激光照射)、联合治疗组(2 mg/kg DOX+50 mg/kg 5-ALA+660 nm激光照射),每周1次,共3次。比较每组小鼠体质量、肿瘤体积、抑瘤率、病理及表皮生长因子受体(EGFR)、缺氧诱导因子1α(HIF-1α)蛋白表达。结果DOX组体质量为(18.16±1.10)g、联合治疗组为(17.93±1.21)g,分别与空白对照组[(20.32±1.34)g]、PDT组[(21.25±1.55)g]相比,体质量均显著下降(t=2.087、2.986、3.014、4.212,均P<0.05),而DOX组与联合治疗组的体质量差异无统计学意义(P>0.05);联合治疗组肿瘤体积为(0.41±0.13)cm^(3),显著低于其他组[PDT组为(0.71±0.13)cm^(3)、DOX组为(0.65±0.19)cm^(3)、空白对照组为(0.98±0.21)cm^(3),t=10.884、8.769、6.182,均P<0.05],而抑瘤率(58.20%,1.10/1.89)显著高于PDT组(27.51%,0.52/1.89)和DOX组(33.86%,0.64/1.89)(t=8.521、8.867,均P<0.05),且病理结果发现联合治疗组凋亡和坏死细胞显著高于其他组;PDT组和联合治疗组与空白对照组和DOX组相比,EGFR和HIF-1α蛋白表达均显著下降(t=2.354、3.287、4.239、5.894,均P<0.05)。结论PDT联合DOX治疗乳腺癌具有疗效好、不良反应小的优点,机制可能与PDT抑制EGFR和HIF-1α蛋白表达有关。Objective To investigate the effect of photosensitizer 5-aminolevulinic acid(5-ALA)and doxorubicin(DOX)in the treatment of breast cancer by randomized controlled trials and its possible mechanism.Methods In October 2020,nude mouse models bearing breast cancer were established by using 4T1 mouse breast cancer cells and BALB/c-nu/nu nude mice.The thirty-two nude mice were divided into a blank control group(without any treatment),a DOX group(2 mg/kg DOX),a photodynamic therapy(PDT)group(50 mg/kg 5-ALA+660 nm laser irradiation),and a combined therapy group(2 mg/kg DOX+50 mg/kg 5-ALA+660 nm laser irradiation),with eight in each group.They were treated once a week for three times.The body weights,tumor volumes,tumor inhibition rates,pathology,and the expressions of epidermal growth factor receptor(EGFR)and hypoxia inducible factor-1α(HIF-1α)were compared between the four group.Results The body weights in the DOX group and the combined therapy group were(18.16±1.10)g and(17.93±1.21)g,which were lower than those in the blank control group[(20.32±1.34)g]and the PDT group[(21.25±1.55)g](t=2.087,2.986,3.014,and 4.212;all P<0.05),but there was no statistical difference between the DOX group and the combined therapy group(P>0.05).The tumor volume of the combined therapy group[(0.41±0.13)cm^(3)]was significantly lower than those in the PDT group[(0.71±0.13)cm^(3)],the DOX group[(0.65±0.19)cm^(3)],and the blank control group[(0.98±0.21)cm^(3)](t=10.884,8.769,and 6.182;all P<0.05).The tumor inhibition rate was 58.20%(1.10/1.89)in the combined therapy group,which was higher than those in the PDT group(27.51%,0.52/1.89)and the DOX group(33.86%,0.64/1.89),(t=8.521 and 8.867,both P<0.05).The pathological results showed that the apoptosis and necrosis cells in the combined therapy group were significantly higher than those in other groups.The protein expressions of EGFR and HIF-1αin the PDT group and the combined therapy group were significantly lower than those in the blank control group and the DOX group(t=2.354,3.287,4.

关 键 词：乳腺癌 5-氨基酮戊酸 阿霉素 光动力疗法 EGFR HIF-1α 

分 类 号：R737.9[医药卫生—肿瘤]