聚合人脐带血红蛋白增敏乳腺癌小鼠化学免疫疗法治疗效果的初步研究  

Therapeutic effect of chemoimmunotherapy on breast cancer sensitized by polymerized human cord hemoglobin in mice:a preliminary study

作　　者：郑诗凡 周文涛[1] 李燊[1] 吴嘉康 游训仪 刘嘉馨[1] 王红[1] ZHENG Shifan;ZHOU Wentao;LI Shen;WU Jiakang;YOU Xunyi;LIU Jiaxin;WANG Hong(Institute of Blood Transfusion,Chinese Academy of Medical Sciences&Peking Union Medical College,Chengdu 610051,China)

机构地区：[1]中国医学科学院北京协和医学院输血研究所,四川成都610052

出　　处：《中国输血杂志》2024年第3期290-296,共7页Chinese Journal of Blood Transfusion

基　　金：中国医学科学院医学与健康科技创新工程项目“血液安全保障及新产品技术研究”(2021-I2M-1-060)。

摘　　要：目的探讨聚合人脐带血红蛋白氧载体(PolyCHb)增强小鼠4T1乳腺癌原位瘤化学免疫疗法敏感性的影响。方法构建4T1乳腺癌原位瘤模型,将15只小鼠随机均分为3组,空白组:无干预;对照组:多柔比星(DOX)+PD-1抑制剂(a-PD-1)治疗,腹腔注射DOX 5 mg·kg^(-1)、1次/周,腹腔注射PD-1抑制剂12.5 mg·kg^(-1)、1次/周;实验组:DOX+a-PD-1+PolyCHb治疗,DOX和a-PD-1用法同上,PolyCHb:尾静脉注射600 mg·kg^(-1)、3次/周;给药周期为4周。给药期间记录肿瘤体积3次/周,绘制各组肿瘤生长曲线并计算抑瘤率。29 d处死小鼠,剥瘤后称瘤重;免疫荧光法检测肿瘤组织中HIF-1α的含量;HE染色观察肿瘤组织病理变化;TUNEL法检测肿瘤细胞凋亡情况;免疫组化法检测肿瘤增殖指标Ki67表达情况。结果与空白组和对照组相比,实验组组肿瘤体积显著减小(P<0.05)、抑瘤率(%)显著提高(P<0.05);实验组肿瘤组织中HIF-1α含量降低(P<0.05);实验组肿瘤组织生长区减少,并伴坏死区增加;各组肿瘤组织细胞凋亡阳性率(%)分别为18.79±0.62、20.68±1.19、41.65±2.99(F=135.2,P<0.001);此外肿瘤增殖指标Ki67结果显示对照组与实验组比较有统计学差异(P<0.05)。结论PolyCHb可以增加乳腺原位瘤小鼠化学免疫疗法的敏感性,其作用机制可能与降低HIF-1α表达,促进细胞凋亡和坏死,抑制肿瘤细胞增殖有关。Objective To investigate the effect of polymerized human cord hemoglobin(PolyCHb)in chemoimmunotherapy for breast cancer in mice.Methods A 4T1 breast cancer in situ tumor model was established,and 15 mice were randomly divided into 3 groups:blank group:no intervention;Control group:doxorubicin+PD-1 inhibitor was given intraperitoneal injection of doxorubicin 5 mg·kg^(-1)once a week and PD-1 inhibitor 12.5 mg·kg^(-1)once a week;Experimental group:DOX+a-PD-1+PolyCHb,the usage of DOX and a-PD-1 was the same as above,PolyCHb:PolyCHb 600 mg·kg^(-1)was injected into the tail vein,three times a week;The administration period was 4 weeks.During the administration,the tumor volume was recorded 3 times per week,the tumor growth curve of each group was drawn and the tumor inhibition rate was calculated.The mice were killed on the 29th day,and the tumor was removed and weighed to calculate the tumor inhibition rate.Immunofluorescence,HE staining,TUNEL method and immunohistochemistry was used to detect the expression of HIF-1α,observe the pathological changes of tumor tissue,detect the apoptosis of tumor cells,and detect the expression of tumor proliferation index Ki67.Results Compared with the blank group and the control group,the tumor volume in the experimental group decreased significantly(P<0.05)and the tumor inhibition rate(%)increased significantly(P<0.05).The content of HIF-1αin tumor tissue in experimental group decreased(P<0.05).In the experimental group,the growth area of tumor tissue decreased,accompanied by the increase of necrosis area;The positive rates(%)of apoptosis in tumor tissues of blank group,control group and experimental group were 18.79±0.62,20.68±1.19 and 41.65±2.99 respectively(F=135.2,P<0.001).In addition,the results of tumor proliferation index Ki67 showed that there was a statistical difference between the control group and the experimental group(P<0.05).Conclusion PolyCHb increases the sensitivity of chemoimmunotherapy in breast cancer mouse model,and the mechanism may be related to the

关 键 词：聚合人脐带血红蛋白 乳腺癌 原位瘤模型 化学免疫疗法 动物实验 

分 类 号：R457.2[医药卫生—治疗学] R331.341[医药卫生—临床医学] R458.8