Ultrasound irradiation microbubble verapamil reverses multidrug resistance of neuroblastoma cells in vitro

陈镜宇; 全学模; 郭振华; 王荞; 唐毅; 王佚

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Ultrasound irradiation microbubble verapamil reverses multidrug resistance of neuroblastoma cells in vitro

更新时间：2026-01-09

- Ultrasound irradiation microbubble verapamil reverses multidrug resistance of neuroblastoma cells in vitro
- Journal of Army Medical University Vol. 32, Issue 16, Pages: 1724-1727(2010)
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  CLC： R739.4;R972.2;R979.1
- Published：2010
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陈镜宇,全学模,郭振华,王荞,唐毅,王佚.超声辐照维拉帕米微泡体外对神经母细胞瘤多药耐药的逆转作用[J].陆军军医大学学报(原第三军医大学学报),2010,32(16):1724-1727.

　Chen Jingyu,Quan Xuemo,Guo Zhenhua,Wang Qiao,Tang Yi,Wang Yi.Ultrasound irradiation microbubble verapamil reverses multidrug resistance of neuroblastoma cells in vitro[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(16):1724-1727.
陈镜宇,全学模,郭振华,王荞,唐毅,王佚.超声辐照维拉帕米微泡体外对神经母细胞瘤多药耐药的逆转作用[J].陆军军医大学学报(原第三军医大学学报),2010,32(16):1724-1727. DOI：

　Chen Jingyu,Quan Xuemo,Guo Zhenhua,Wang Qiao,Tang Yi,Wang Yi.Ultrasound irradiation microbubble verapamil reverses multidrug resistance of neuroblastoma cells in vitro[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(16):1724-1727. DOI：

摘要

目的探讨超声辐照维拉帕米（verpamil，VER）微泡逆转肿瘤多药耐药的作用及机制。方法制备包裹维拉帕米的乳酸-羟基乙酸共聚物（VER-PLGA）超声微泡造影剂；通过长春新碱（VCR）多次小剂量递增诱导法建立神经母细胞瘤耐药株（SK-N-SH/VCR），并检测其耐药性；根据处理因素不同分为6组：A：空白对照组（SK-N-SH/VCR培养组)，B：SK-N-SH/VCR+VER(50 μg/ml)组，C：SK-N-SH/VCR+VER(250 μg/ml)组，D：SK-N-SH/VCR+超声辐照组，E：SK-N-SH/VCR+PLGA微泡+超声辐照组，F：SK-N-SH/VCR+VER-PLGA微泡(VER 50 μg/ml)+超声辐照组。48 h后，利用RT-PCR和免疫组织化学染色法(ICC)检测各组细胞中MDR1基因及P-gp的表达水平，评估VER在不同处理组中逆转肿瘤细胞耐药的效果。结果 ①成功制备包裹维拉帕米的VER-PLGA微泡造影剂，包封率为32%；②成功建立神经母细胞瘤耐药株SK-N-SH/VCR，MTT法证实其对不同化疗药物的耐药倍数是野生株的2.3～5.4倍；③ ICC证实耐药株高表达MDR1基因；④RT-PCR及免疫组化法检测发现MDR1基因在F组中的光密度值及P-gp表达水平较其他组明显降低（P0.05）。结论超声辐照包裹小剂量维拉帕米的微泡可有效逆转肿瘤多药耐药。

Abstract

Objective To study the effects of ultrasound irradiation microbubbles with verpamil (VER) on reversing tumor multidrug resistance. Methods VER - PLGA microbubbles were prepared with double emulsion and freeze drying techniques. The neuroblastoma cell line SK - N - SH/VCR with multidrug resistance (MDR) phenotype was established by inducing with small - doses of VCR. Then the cells were divided into 6 groups according to different trea

tments

that is

group A: SK - N - SH/VCR

group B: SK - N - SH/VCR+VER (50 μ g/ml)

group C: SK - N - SH/VCR+VER (250 μ g/ml)

group D: SK - N - SH/VCR+ultrasound

group E: SK - N - SH/VCR+PLGA+ultrasound

group F: SK - N - SH/VCR+VER - PLGA (50 μ g/ml)+ultrasound. RT - PCR and immunocytochemical staining were used to detect the expression levels of MDR1 gene and P - gp respectively. And the effects of VER on reversing multidrug resistance of tumor in different groups were evaluated. Results The VER - PLGA microbubbles were prepared successfully

and the encapsulated rate was 32%. SK - N - SH/VCR cells with MDR phenotype were established and the resistance index (RI) was 2.3 to 5 . 4 times to different chemotherapy drugs when compared with the wild cells. Compared with others

the level of MDR1 gene was the most lowest in group F (

0 . 05). The expression levels of P - gp and MDR1 gene were the lowest in group F among the all 6 groups (

0 . 05). Conclusion Ultrasound irradiation microbubbles enhance the effects of verapamil to reverse the multidrug resistance of tumor. 15 Refs. In Chinese.

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