载拉帕替尼靶向超声微泡联合高强度聚焦超声对HER-2阳性人乳腺癌SK-BR-3细胞作用的实验研究  

Experimental Study on the Effect of Lapatinib-loaded Targeted Ultrasound Microbubbles Combined with High-intensity Focused Ultrasound on HER-2 Positive Human Breast Cancer SK-BR-3 Cells

作　　者：宋昭君 骆娟 郑佳状[1] 汪凡栋[1] 陈宇[1] 刘元彬[1] SONG Zhao-jun;LUO Juan;ZHENG Jia-zhuang;WANG Fan-dong;CHEN Yu;LIU Yuan-bin(Spine Surgery Department of Suining Central Hospital,Suining 629000,Sichuan,China)

机构地区：[1]遂宁市中心医院骨科中心,四川遂宁629000

出　　处：《医学信息》2024年第10期76-82,共7页Journal of Medical Information

基　　金：四川省卫健委卫生健康科研课题普及应用项目(编号:19PJYY0041)。

摘　　要：目的探讨携HER-2抗体载拉帕替尼新型靶向纳米超声微泡联合高强度聚焦超声(HIFU)对人乳腺癌SK-BR-3细胞的生物学作用。方法采用机械振荡法制备携HER-2抗体载拉帕替尼新型靶向纳米超声微泡体外培养HER-2(+)人乳腺癌SK-BR-3细胞珠,分为4组。HER-2抗体载拉帕替尼超声微泡为A组、单纯载拉帕替尼超声微泡+HER-2抗体为B组、携HER-2抗体空白超声微泡为C组、空白超声微泡为D组。载拉帕替尼靶向纳米超声微泡与细胞联合培养,联合HIFU作用,采用流式细胞技术、CCK-8实验、western blot实验在不同时间点观察载拉帕替尼靶向纳米超声微泡联合HIFU对SK-BR-3细胞生物学效应。结果本实验所制备的携HER-2抗体载拉帕替尼新型靶向纳米超声微泡的平均粒径为(204.80±116.30)nm,Zeta电位为(-5.42±4.11)mV,包封率为(35.20±1.58)%。体外细胞寻靶实验结果显示,携HER-2抗体载拉帕替尼新型靶向纳米超声微泡联合HIFU作用与SK-BR-3细胞的结合能力高于其他三组(P<0.05);流式细胞结果显示A组能有效促进SK-BR-3细胞凋亡,CCK-8实验结果显示A组能明显抑制SK-BR-3细胞增殖,同时A组细胞凋亡相关蛋白Bcl-2表达升高,侵袭相关蛋白MMP-2表达降低(P<0.05)。结论携HER-2抗体载拉帕替尼超声微泡联合HIFU消融作用能有效地将拉帕替尼递送入SK-BR-3细胞,并能有效抑制SK-BR-3细胞的生长,促进其凋亡。Objective To explore the effect of lapatinib-loaded targeted ultrasound microbubbles combined with high-intensity focused ultrasound(HIFU)on HER-2 positive human breast cancer SK-BR-3 cells.Methods The HER-2(+)human breast cancer SK-BR-3 cell beads were cultured in vitro by using a novel targeted ultrasound microbubbles carrying HER-2 antibody and lapatinib-loaded by mechanical oscillation method,which were divided into 4 groups.HER-2 antibody and lapatinib-loaded targeted ultrasound microbubbles were group A,simple lapatinib-loaded targeted ultrasound microbubbles+HER-2 antibody were group B,HER-2 antibody and blank-loaded ultrasound microbubbles were group C,and blank ultrasound microbubbles were group D.Lapatinib-loaded targeted ultrasound microbubbles were co-cultured with cells and combined with HIFU.Flow cytometry,CCK-8 assay and western blot assay were used to observe the biological effects of Lapatinib-loaded targeted ultrasound microbubbles combined with HIFU on SK-BR-3 cells at different time points.Results The mean diameter of the lapatinib-loaded targeted ultrasound microbubbles was(204.8±116.3)nm,the Zeta potential was(-5.42±4.11)mV,and the encapsulation efficiency was(35.20±1.58)%.The results of in vitro cell targeting experiments showed that the binding ability of the lapatinib-loaded targeted ultrasound microbubbles with HER-2 antibody and HIFU to SK-BR-3 cells was higher than that of the other three groups(P<0.05).The results of flow cytometry showed that group A could effectively promote the apoptosis of SK-BR-3 cells.The results of CCK-8 assay showed that group A could significantly inhibit the proliferation of SK-BR-3 cells.At the same time,the expression of apoptosis-related protein Bcl-2 increased and the expression of invasion-related protein MMP-2 decreased in group A(P<0.05).Conclusion Lapatinib-loaded targeted ultrasound microbubbles with HER-2 antibody and HIFU can effectively deliver lapatinib to SK-BR-3 cells,effectively inhibit the growth of SK-BR-3 cells,and promote their apoptos

关 键 词：超声微泡 高强度聚焦超声 拉帕替尼 乳腺癌 

分 类 号：R9737.9[医药卫生—药品]