黄芩苷改善肿瘤缺氧微环境抑制乳腺癌移植瘤的生长  

Baicalin Improves Tumor Hypoxic Microenvironment and Inhibits the Growth of Breast Cancer Xenograft

作　　者：戴新军 黄立中[1] 肖玉洁[1] 龚辉 田雪飞[1] Dai Xinjun;Huang Lizhong;Xiao Yujie;Gong Hui;Tian Xuefei(College of Integrated Traditional Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410000,China)

机构地区：[1]湖南中医药大学中西医结合学院,长沙410000

出　　处：《世界科学技术-中医药现代化》2022年第2期526-533,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：湖南中医药大学校级科研基金一般项目(2019XJJJ007):基于“火郁发之”探讨黄芩苷治疗三阴乳腺癌的作用基质,负责人:肖玉洁。

摘　　要：目的通过观察黄芩苷对乳腺癌组织毛细血管通透性(Capillary Vessel Permeability,CVP)、赖氨酰氧化酶(Lysyl Oxidase,LOX)及血清丙二醛(Malondialdehyde,MDA)等相关指标的影响,探讨黄芩苷可能的抗乳腺癌作用机制。方法通过在裸鼠皮下接种MDA-MB-231乳腺癌细胞株建立乳腺癌移植瘤模型;实验分为模型组、黄芩苷组、阿霉素组、黄芩苷+阿霉素组。于接种第7日开始:黄芩苷组每天灌胃黄芩苷水溶液(100 mg·kg^(-1)),连续14天;阿霉素组每3天腹腔注射一次阿霉素(5mg·kg^(-1)),共用药5次;模型组每天灌胃生理盐水(10 mL·kg^(-1)),连续14天;黄芩苷+阿霉素组每天灌胃黄芩苷水溶液(100 mg·kg^(-1)),连续14天,并每3天腹腔注射一次阿霉素5 mg·kg^(-1),共5次。给药期间监测移植瘤体积;紫外可见分光光度计620 nm下测OD值来反映黄芩苷对肿瘤毛细血管通透性的影响;硫代巴比妥酸(Thiobarbituric acid,TBA)比色法检测黄芩苷对裸鼠血清中丙二醛(MDA)的影响;免疫组化染色法检测乳腺癌组织中赖氨酰氧化酶(LOX)的表达情况。结果①与模型组比较,黄芩苷组、阿霉素组、黄芩苷+阿霉素组瘤体重量均明显减轻(P<0.05);黄芩苷+阿霉素组瘤体重量较阿霉素组明显减轻(P<0.05)。②与模型组比较,黄芩苷组降低乳腺癌组织毛细血管的通透性,而阿霉素组则增加肿瘤组织中毛细血管的通透性,差异均具有统计学意义(P<0.05)。③黄芩苷组能够明显抑制荷瘤裸鼠血清MDA的表达,与模型组比较差异有显著统计学意义(P<0.01);阿霉素组促进MDA的表达,与模型组比较差异有统计学意义;黄芩苷+阿霉素组促进MDA的表达,与模型组比较差异无统计学意义。④与模型组比较,黄芩苷组裸鼠乳腺癌组织LOX的表达显著下调(P<0.01),阿霉素组肿瘤组织中LOX表达增加(P<0.05);黄芩苷+阿霉素组能下调裸鼠乳腺癌组织LOX的表达,与模型组比较差异无统计学意义。结论黄芩Objective To explore the possible mechanism of anti-breast cancer action of baicalin by observing the effects of baicalin on capillary permeability(CVP),lysine oxidase(LOX)and serum malondialdehyde(MDA)of breast cancer tissue.Methods The model of breast cancer transplantation was established by subcutaneously inoculating MDA-MB-231 breast cancer cell line in nude mice;The experiment was divided into model group,baicalin group,adriamycin group,and baicalin+adriamycin group.From the 7^(th) day of vaccination,baicalin group was given baicalin aqueous solution(100 mg·kg^(-1))every day for 14 consecutive days;The adriamycin group was intraperitoneally injected with adriamycin(5 mg·kg^(-1))once every 3 days for a total of 5 times;Model group was intragastrically given normal saline(10 ml·kg^(-1))every day for 14 consecutive days;Baicalin+adriamycin group was given baicalin injection(100mg·kg^(-1))every day for 14 consecutive days,and adriamycin 5mg·kg^(-1) was injected intraperitoneally every 3 days for 5 times.The volume of graft was monitored during administration;The influence of baicalin on the permeability of tumor capillary was reflected by measuring the OD value under the UV visible spectrophotometer at 620 nm;The effect of baicalin on serum malondialdehyde(MDA)in nude mice was determined by thiobarbituric acid(TBA)colorimetry;The expression of lysyl oxidase(LOX)in breast cancer tissues was detected by immunohistochemical staining.Results①Compared with model group,the tumor weight of baicalin group,adriamycin group and baicalin+adriamycin group were significantly decreased(P<0.05);The tumor weight of baicalin+adriamycin group was significantly decreased compared with adriamycin group(P<0.05).②Compared with the model group,the baicalin group decreased the capillary permeability of breast cancer tissue,while the adriamycin group increased the capillary permeability of breast cancer tissue,with statistical significance(P<0.05).③Baicalin group could significantly inhibit the expression of MDA in serum of

关 键 词：黄芩苷 乳腺癌 赖氨酰氧化酶 丙二醛 毛细血管通透性 肿瘤缺氧微环境 

分 类 号：R285.5[医药卫生—中药学]