Butterworth Michael, Pettitt Andrew, Varadarajan Shankar, Cohen Gerald M
Departments of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GE, UK.
Department of Pharmacology, University of Liverpool, Liverpool L69 3GE, UK.
Br J Cancer. 2016 Mar 15;114(6):638-41. doi: 10.1038/bjc.2016.49. Epub 2016 Mar 8.
Anti-apoptotic BCL-2 family members antagonise apoptosis by sequestering their pro-apoptotic counterparts. The balance between the different BCL-2 family members forms the basis of BH3 profiling, a peptide-based technique used to predict chemosensitivity of cancer cells. Recent identification of cell-permeable, selective inhibitors of BCL-2, BCL-XL and MCL-1, further facilitates the determination of the BCL-2 family dependency of cancer cells.
We use BH3 profiling in combination with cell death analyses using a chemical inhibitor toolkit to assess chemosensitivity of cancer cells.
Both BH3 profiling and the inhibitor toolkit effectively predict chemosensitivity of cells addicted to a single anti-apoptotic protein but a combination of both techniques is more instructive when cell survival depends on more than one anti-apoptotic protein.
The inhibitor toolkit provides a rapid, inexpensive and simple means to assess the chemosensitivity of tumour cells and in conjunction with BH3 profiling offers much potential in personalising cancer therapy.
抗凋亡BCL-2家族成员通过隔离其促凋亡对应物来拮抗细胞凋亡。不同BCL-2家族成员之间的平衡构成了BH3分析的基础，这是一种基于肽的技术，用于预测癌细胞的化疗敏感性。最近发现的可渗透细胞的BCL-2、BCL-XL和MCL-1选择性抑制剂，进一步促进了对癌细胞BCL-2家族依赖性的测定。
我们将BH3分析与使用化学抑制剂工具包的细胞死亡分析相结合，以评估癌细胞的化疗敏感性。
BH3分析和抑制剂工具包都能有效预测对单一抗凋亡蛋白成瘾的细胞的化疗敏感性，但当细胞存活依赖于一种以上抗凋亡蛋白时，两种技术结合使用更具指导意义。
抑制剂工具包提供了一种快速、廉价且简单的方法来评估肿瘤细胞的化疗敏感性，与BH3分析相结合在癌症治疗个性化方面具有很大潜力。
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