Hind C K, Carter M J, Harris C L, Chan H T C, James S, Cragg M S
Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
Int J Biochem Cell Biol. 2015 Feb;59:94-102. doi: 10.1016/j.biocel.2014.11.015. Epub 2014 Dec 6.
Bfl-1 is a pro-survival Bcl-2 family member overexpressed in a subset of chemoresistant tumours, including melanoma. Here, we characterised the expression and regulation of Bfl-1 in normal and malignant melanocytes and determined its role in protecting these cells from chemotherapy-induced apoptosis. Bfl-1 was mitochondrially resident in both resting and apoptotic cells and experienced regulation by the proteasome and NFκB pathways. siRNA-mediated knockdown enhanced sensitivity towards various relevant drug treatments, with forced overexpression of Bfl-1 protective. These findings identify Bfl-1 as a contributor towards therapeutic resistance in melanoma cells and support the use of NFκB inhibitors alongside current treatment strategies.
Bfl-1是一种促生存的Bcl-2家族成员，在包括黑色素瘤在内的一部分化疗耐药肿瘤中过表达。在此，我们对正常和恶性黑素细胞中Bfl-1的表达及调控进行了表征，并确定了其在保护这些细胞免受化疗诱导的凋亡中的作用。Bfl-1定位于静息细胞和凋亡细胞的线粒体中，并受蛋白酶体和NFκB途径的调控。siRNA介导的敲低增强了对各种相关药物治疗的敏感性，而Bfl-1的强制过表达具有保护作用。这些发现确定Bfl-1是黑色素瘤细胞治疗耐药的一个促成因素，并支持在当前治疗策略中联合使用NFκB抑制剂。
