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超声空化效应增强西妥昔单抗对三阴性乳腺癌的抑制作用
Ultrasound Cavitation Enhanced the Inhibitory Effect of Cetuximab on Triple-negative Breast Cancer
【摘要】 目的探讨超声破坏微泡引起的空化效应对西妥昔单抗抑制三阴性乳腺癌(TNBC)作用的影响。方法建立裸鼠皮下TNBC移植瘤模型40只,采用数字表法随机分为超声辐照微泡+西妥昔单抗组(A组)、西妥昔单抗组(B组)、超声辐照微泡组(C组)、对照组(D组),每组10只,每天给予相应治疗1次,连续7天;于首次治疗前及末次治疗后第1天行二维超声及超声造影检查,随后取肿瘤组织行HE染色观察病理变化、TUNEL法检测细胞凋亡,比较各组肿瘤体积、造影峰值强度(PI)、曲线下面积(AUC)、凋亡指数(AI)的差异。结果治疗后,A、B、C组肿瘤体积均小于D组(P <0.05),其中A组体积最小(P <0.05);A组超声造影PI、AUC值均低于B、C、D组(P <0.05),C组AUC值低于D组(P <0.05),其余各组PI及AUC值组间比较,差异无统计学意义(P>0.05); A组肿瘤组织见大片坏死,AI值高于其余各组(P <0.05)。结论超声空化效应增强西妥昔单抗对TNBC的抑制作用,两者联用显著降低肿瘤血液灌注,促进细胞凋亡及组织坏死。
【Abstract】 Objective To investigate the influence of cavitation induced by ultrasound-targeted microbubbles destruction on cetuximab inhibiting triple-negative breast cancer( TNBC). Methods Forty nude mice models of subcutaneous TNBC were established and randomly divided into four groups: ultrasound-targeted microbubbles destruction + cetuximab group( group A),cetuximab group( group B),ultrasound-targeted microbubbles destruction group( group C),and control group( group D). Each group was given corresponding treatment once a day for 7 days. Two-dimensional ultrasound and contrast-enhanced ultrasound were performed before the first treatment and on the first day after the last treatment,and then HE staining was taken to observe the pathological changes and TUNEL method to detect apoptosis. The differences of peak intensity( PI) and area under the curve( AUC) of contrast-ultrasound curve,tumor volume and apoptotic index( AI) were compared between each group. Results The tumor volume values of group A,B and C were smaller than that of group D( P < 0. 05) after treatment,among which group A had the smallest volume value( P < 0. 05). After treatment,the PI and AUC values of group A were lower than those of other groups( P < 0. 05),and AUC value of group C was lower than that of group D( P < 0. 05),while values of PI and AUC among other groups had no significant difference( P > 0. 05). HE staining of tumor tissues in group A showed large necrosis after treatment,and AI value of group A was higher than that of other groups( P < 0. 05).Conclusion Ultrasound cavitation enhanced the inhibitory effect of cetuximab on TNBC. The combination of the two could significantly reduce tumor blood perfusion,promote cell apoptosis and tissue necrosis.
【Key words】 Ultrasound cavitation; Microbubbles; Cetuximab; Targeted therapy; Triple-negative breast cancer;
- 【文献出处】 医学研究杂志 ,Journal of Medical Research , 编辑部邮箱 ,2020年11期
- 【分类号】R445.1;R737.9
- 【被引频次】1
- 【下载频次】226