低强度超声联合托泊替康诱导人肝癌细胞凋亡的研究

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (12): 1384-1388.

低强度超声联合托泊替康诱导人肝癌细胞凋亡的研究

邱日想¹, 王燕莉¹, 陈洋娣¹, 林雁², 杨凤², 陈智毅²

¹广州医学院第三附属医院药学部, ²广州医学院第三附属医院医学超声科,广州 510150,广东

收稿日期:2012-08-08 修回日期:2012-11-14 出版日期:2012-12-26 发布日期:2012-12-31
通讯作者: 陈智毅,通信作者,男,博士,副主任医师,研究方向:超声分子影像学。E-mail: winchen@vip.126.com
作者简介:邱日想,男,本科,主管药师,研究方向:载药/基因微泡制备技术和分子影像药学。E-mail: 1320229836@qq.com
基金资助:
广东省科技厅项目(2012B050300026); 广州市科信局科研项目(12C22021645); 广州市教育局科研项目(10A242); 广东省自然科学基金项目(S2012040006593)

Synergistic combination of topotecan and low-intensity ultrasound to enhance HepG2 cell apoptosis

QIU Ri-xiang¹, WANG Yan-li¹, CHEN Yang-di¹, LIN YAN², YANG Feng², CHEN Zhi-yi²

¹Department of Pharmacy, ²Department of Medical Ultrasound, the Third Affiliated Hospital of Guangzhou Medical College, Guangzhou 510150, Guangdong, China

Received:2012-08-08 Revised:2012-11-14 Online:2012-12-26 Published:2012-12-31

摘要/Abstract

摘要： 目的: 研究低强度超声联合托泊替康诱导人肝癌细胞(HepG2)凋亡的协同效应以及相关的机制。方法: 应用HepG2,实验分为托泊替康处理组、超声处理组、联合治疗组(托泊替康+超声),评估细胞生存活力、细胞凋亡,胞内托泊替康累积及空化效应。结果: 当超声强度为 0.8 W/cm² 及以上时,协同托泊替康能明显诱导HepG2细胞凋亡,1.0 W/cm² 超声辐照联合托泊替康时细胞凋亡率为 12.88%,空化效应在凋亡诱导实验中促进了托泊替康胞内渗入,增加胞内积累。结论: 联合低强度超声能增强托泊替康的凋亡诱导效应,空化效应是其协同增强的主要机制。

关键词: HepG2, 低强度超声, 托泊替康, 细胞凋亡

Abstract: AIM: To study the combined effects of low-intensity pulsed ultrasound (LIPUS) and topotecan (TOP) on cell apoptosis induction of HepG2 cells and the mechanisms involved. METHODS: Human liver cancer HepG2 cells were used for the experiments. Experiments were conducted in 4 groups: non-treated, TOP treated, ultrasound treated, and combined (TOP+LIPUS). The viability was evaluated by trypan blue dye exclusion test and apoptosis and incorporation of TOP was assessed by flow cytometry. Involvement of sonoporation in molecular incorporation was evaluated using FITC-dextran. RESULTS: Synergistic enhancement in cell killing and additive enhancement in induction of apoptosis were observed at and above 0.8W/cm². Incorporation of TOP was increased 12.88% in combined group (vs. TOP) at 1.0W/cm². Increasing in incorporation of the TOP by cavitation and ultrasound were the mechanisms of enhancements. CONCLUSION: Combination of TOP and LIPUS can enhance the effect of apoptosis induction, and cavitation is the main mechanism for their synergistic.

Key words: HepG2, Low-intensity ultrasound, Topotecan, Apoptosis

中图分类号:

R965.2

邱日想, 王燕莉, 陈洋娣, 林雁, 杨凤, 陈智毅. 低强度超声联合托泊替康诱导人肝癌细胞凋亡的研究[J]. 中国临床药理学与治疗学, 2012, 17(12): 1384-1388.

QIU Ri-xiang, WANG Yan-li, CHEN Yang-di, LIN YAN, YANG Feng, CHEN Zhi-yi. Synergistic combination of topotecan and low-intensity ultrasound to enhance HepG2 cell apoptosis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(12): 1384-1388.

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