Granville D J, Jiang H, An M T, Levy J G, McManus B M, Hunt D W
QLT Photo Therapeutics, Vancouver, BC, Canada.
Br J Cancer. 1999 Jan;79(1):95-100. doi: 10.1038/sj.bjc.6690017.
Treatment with the photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) followed by irradiation with visible light induces apoptosis in human acute myelogenous leukaemia HL-60 cells. Photoactivation of BPD-MA induces procaspase 3 (CPP32/Yama/apopain) and procaspase 6 (Mch2) cleavage into their proteolytically active subunits in these cells. The Bcl-2 proto-oncogene product has been shown to protect cells from a number of proapoptotic stimuli. In the present study, the influence of Bcl-2 overexpression on cellular resistance to photoactivation of BPD-MA was studied. Overexpression of Bcl-2 in HL-60 cells prevented apoptosis-related events including caspase 3 and 6 activation, poly(ADP-ribose) polymerase cleavage and the formation of hypodiploid DNA produced by BPD-MA (0-200 ng ml(-1)) and light. However, Bcl-2 overexpression was less effective at preventing cell death that occurred after photoactivation at high levels (50-100 ng ml(-1)) compared with lower doses (10-25 ng ml(-1)) of BPD-MA. These results indicate that caspase 3 and 6 activation and their regulation by Bcl-2 may play important roles in photodynamic therapy (PDT)-induced cell killing.
用光敏剂苯并卟啉衍生物单酸环A（BPD - MA，维替泊芬）处理，随后用可见光照射，可诱导人急性髓性白血病HL - 60细胞凋亡。在这些细胞中，BPD - MA的光激活可诱导半胱天冬酶原3（CPP32/Yama/凋亡蛋白酶）和半胱天冬酶原6（Mch2）裂解为其蛋白水解活性亚基。已证明Bcl - 2原癌基因产物可保护细胞免受多种促凋亡刺激。在本研究中，研究了Bcl - 2过表达对细胞抵抗BPD - MA光激活的影响。HL - 60细胞中Bcl - 2的过表达可预防凋亡相关事件，包括半胱天冬酶3和6的激活、聚（ADP - 核糖）聚合酶的裂解以及由BPD - MA（0 - 200 ng ml(-1)）和光照产生的亚二倍体DNA的形成。然而，与较低剂量（10 - 25 ng ml(-1)）的BPD - MA相比，Bcl - 2过表达在预防高水平（50 - 100 ng ml(-1)）光激活后发生的细胞死亡方面效果较差。这些结果表明半胱天冬酶3和6的激活及其受Bcl - 2的调节可能在光动力疗法（PDT）诱导的细胞杀伤中起重要作用。
