Aroui Sonia, Ram Narendra, Appaix Florence, Ronjat Michel, Kenani Abderraouf, Pirollet Fabienne, De Waard Michel
INSERM, U836, Calcium Channels, Functions and Pathologies, BP 170, Grenoble Cedex 9, 38042, France.
Pharm Res. 2009 Apr;26(4):836-45. doi: 10.1007/s11095-008-9782-1. Epub 2008 Dec 13.
The aim of this study is to overcome tumour cell resistance that generally develops after administration of commonly used anti-cancer drugs, such as doxorubicin.
Recently, cell penetrating peptides have been used for their ability to deliver non-permeant compounds into cells. One such cell penetrating peptide, maurocalcine, has been isolated from the venom of a Tunisian scorpion. Herein, we report the effects of doxorubicin covalently coupled to an analogue of maurocalcine on drug-sensitive or drug-resistant cell lines MCF7 and MDA-MB 231.
We demonstrated the in vitro anti-tumoral efficacy of the doxorubicin maurocalcine conjugate. On a doxorubicin-sensitive cancer cell line, the maurocalcine-conjugated form appears slightly less efficient than doxorubicin itself. On the contrary, on a doxorubicin-resistant cancer cell line, doxorubicin coupling allows to overcome the drug resistance. This strategy can be generalized to other cell penetrating peptides since Tat and penetratin show similar effects.
We conclude that coupling anti-tumoral drugs to cell penetrating peptides represent a valuable strategy to overcome drug resistance.
本研究的目的是克服在施用常用抗癌药物(如阿霉素)后通常产生的肿瘤细胞耐药性。
最近,细胞穿透肽因其能够将非渗透性化合物递送至细胞内的能力而被使用。一种这样的细胞穿透肽,毛喉素,已从突尼斯蝎子的毒液中分离出来。在此,我们报告了与毛喉素类似物共价偶联的阿霉素对药物敏感或耐药细胞系MCF7和MDA-MB 231的影响。
我们证明了阿霉素-毛喉素缀合物的体外抗肿瘤功效。在阿霉素敏感的癌细胞系上,毛喉素缀合形式的效率似乎略低于阿霉素本身。相反,在阿霉素耐药的癌细胞系上,阿霉素偶联能够克服耐药性。由于Tat和穿膜肽显示出类似的效果,该策略可推广到其他细胞穿透肽。
我们得出结论,将抗肿瘤药物与细胞穿透肽偶联是克服耐药性的一种有价值的策略。