摘要
目的:观察低频率超声空化效应对人乳腺癌细胞株MCF-7/DOX多药耐药的逆转作用,并探讨其逆转肿瘤多药耐药的机制。方法:以不同的超声辐射时间照射MCF-7/S、MCF-7/DOX细胞,采用MTT法筛选出非细胞毒剂量的超声照射时间。以无毒剂量的超声照射联合不同浓度的DOX,比较单独DOX组与联合组MCF-7/DOX细胞对DOX的IC_(50)值有无明显差异,从而判断低频率超声的增敏作用,并计算增敏倍数和相对逆转效率。用流式细胞仪检测细胞凋亡、细胞内阿霉素的浓度。结果:低频率超声辐射对MCF-7/DOX细胞具有一定的细胞毒作用,其非细胞毒辐射时间是10s。非细胞毒性的超声辐射可显著增加阿霉素对MCF-7/DOX细胞的抑制率(从21.65%±0.05%升至43.13%±0.19%),可显著降低阿霉素对MCF-7/DOX细胞的IC_(50)(从61.08±0.27μg/mL降至28.12±5.94μg/mL);对MCF-7细胞的抑制率(从66.47%±0.02%升至67.25%±0.20%)及IC_(50)(从0.84±0.07μg/mL降至0.802±0.03μg/mL)无明显的影响。低频率超声对MCF-7/DOX细胞的逆转倍数为2.17倍,相对逆转效率为:54.71%。流式细胞仪检测结果显示:单独应用DOX,MCF-7细胞的凋亡率为33.99%,MCF-7/DOX细胞的凋亡率为4.4%,低频率超声与DOX合用后,MCF-7/DOX凋亡率为13.70%。低频率超声处理后,MCF-7/DOX细胞内DOX浓度显著增加,峰值明显右移,但尚不能达到敏感细胞的水平。结论:低频率超声可部分逆转人乳腺癌MCF-7/DOX细胞对阿霉素的耐药性,其逆转机制考虑为低频率超声空化效应增加细胞膜的通透性,增加肿瘤细胞内抗肿瘤药物的浓度,从而杀灭耐药的肿瘤细胞,逆转肿瘤耐药性。
Objective： To investigate the effects and mechanism of low-frequency ultrasound in reversing multidrug resistance （MDR） in the MCF-7/DOX cell line. Methods： MTT assay was used to detect the cytotoxic effect of low-frequency ultrasound and the sensitivity to Adriamycin of the MCF-7/DOX cell line. The apoptosis and concentration of Adriamycin in the cells were detected by flow cytometry （FCM）. Results： Low-frequency ultrasound had a definite cytotoxic effect on MCF-7 and MCF-7/DOX cells. The non-cytotoxic time of low-frequency ultrasound was 10 seconds. The non-cytotoxic low-frequency ultrasound significantly increased the inhibitory rate and decreased the half-maximal inhibitory concentration （IC50） value of Adriamycin in the MCF-7/DOX cell line. The IC50 was significantly reduced from 61.08±0.27μg/mL to 28.12± 5.94μg/mL. The non-cytotoxic low-frequency ultrasound could partly reverse MDR in MCF-7/DOX cells by 2.17-fold increase. FCM suggested that low-frequency ultrasound combined with DOX could significantly increase the intracellular concentration of Adriamycin and the apoptosis of MCF-7/DOX. Conclusion： Low-frequency ultrasound can enhance the cytotoxicity of DOX and partially reverse the DOX resistance of MCF-7/DOX. The mechanism may be related to an increase in the permeability of the cell membrane and the concentration of intracellular DOX and may promote the apoptosis of MCF-7/ DOX.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第10期546-549,共4页
Chinese Journal of Clinical Oncology
基金
国家十五科技攻关项目资助(编号:2004BA706803-01)~~
关键词
低频率超声
空化效应
多药耐药
Low-frequency ultrasound
Cavitation effect
Multi-drug resistance
