State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Biomaterials. 2013 Jun;34(18):4452-65. doi: 10.1016/j.biomaterials.2013.02.066. Epub 2013 Mar 18.
The recurrence of breast cancer is associated with drug-resistance of cancer stem cells (CSCs), while overexpression of cell membrane ATP-binding cassette (ABC) transporters and resistance of mitochondrial apoptosis-related proteins are responsible for the drug-resistance of CSCs. The targeting berberine liposomes were developed to modulate the resistant membrane and mitochondrial proteins of breast CSCs for the treatment and prevention of breast cancer relapse. Evaluations were performed on human breast CSCs and CSC xenografts in nude mice. The targeting berberine liposomes were shown to cross the CSC membrane, inhibit ABC transporters (ABCC1, ABCC2, ABCC3, ABCG2) and selectively accumulate in the mitochondria. Furthermore, the pro-apoptotic protein Bax was activated while the anti-apoptotic protein Bcl-2 was inhibited resulting in opening of the mitochondrial permeability transition pores, release of cytochrome c, and activation of caspase-9/caspase-3 enzymes. Significant efficacy of the administrations in mice was observed, indicating that the targeting berberine liposomes are a potential therapy for the treatment and prevention of breast cancer relapse arising from CSCs.
乳腺癌的复发与癌症干细胞（CSC）的耐药性有关，而细胞膜三磷酸腺苷结合盒（ABC）转运蛋白的过度表达和线粒体凋亡相关蛋白的耐药性是 CSC 耐药性的原因。靶向小檗碱脂质体的开发是为了调节乳腺癌 CSC 的耐药性膜和线粒体蛋白，以治疗和预防乳腺癌的复发。在人乳腺癌 CSC 和裸鼠的 CSC 异种移植中进行了评估。靶向小檗碱脂质体被证明可以穿过 CSC 膜，抑制 ABC 转运蛋白（ABCC1、ABCC2、ABCC3、ABCG2）并选择性地积聚在线粒体中。此外，促凋亡蛋白 Bax 被激活，而抗凋亡蛋白 Bcl-2 被抑制，导致线粒体通透性转换孔打开，细胞色素 c 释放，并激活 caspase-9/caspase-3 酶。在小鼠中观察到给药的显著疗效，表明靶向小檗碱脂质体是治疗和预防 CSC 引起的乳腺癌复发的一种潜在疗法。
