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
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
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 apoptosis.Lapatinib-loaded targeted ultrasound microbubbles combined with HIFU ablation will provide a new and safe method for the treatment of breast cancer and its metastasis.
关键词
超声微泡/高强度聚焦超声/拉帕替尼/乳腺癌
Key words
Ultrasonic microbubbles/High-intensity focused ultrasound/Rapatinib/Breast cancer
维普
万方数据