Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany.
Department of Infectious Diseases and Pulmonary Medicine, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany.
Int J Mol Med. 2018 Jul;42(1):534-546. doi: 10.3892/ijmm.2018.3620. Epub 2018 Apr 16.
Photodynamic therapy (PDT) has emerged as an effective and minimally invasive cancer treatment modality. In the present study, two novel phthalocyanines, tetra‑triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) and dihydroxy‑2,9(10),16(17),23(24)‑tetrakis(4,7,10‑trioxaundecan‑1‑sulfonyl) silicon phthalocyanine (Pc32), were investigated as photosensitizers (PS) for PDT of cholangiocarcinoma (CC). ZnPc showed a pronounced dose‑dependent and predominantly cytoplasmic accumulation in EGI‑1 and TFK‑1 CC cell lines. Pc32 also accumulated in the CC cells, but this was less pronounced. Without photoactivation, the PS did not exhibit any antiproliferative or cytotoxic effects. Upon photoactivation, ZnPc induced the formation of reactive oxygen species (ROS) and immediate phototoxicity, leading to a dose‑dependent decrease in cell proliferation, and an induction of mitochondria‑driven apoptosis and cell cycle arrest of EGI‑1 and TFK‑1 cells. Although photoactivated Pc32 also induced ROS formation in the two cell lines, the extent was less marked, compared with that induced by ZnPc‑PDT, and pronounced antipoliferative effects occurred only in the less differentiated EGI‑1 cells, whereas the more differentiated TFK‑1 cells did not show sustained growth inhibition upon Pc32‑PDT induction. In vivo examinations on the antiangiogenic potency of the novel PS were performed using chorioallantoic membrane (CAM) assays, which revealed reduced angiogenic sprouting with a concomitant increase in nonperfused regions and degeneration of the vascular network of the CAM following induction with ZnPc‑PDT only. The study demonstrated the pronounced antiproliferative and antiangiogenic potency of ZnPc as a novel PS for PDT, meriting further elucidation as a promising PS for the photodynamic treatment of CC.
光动力疗法 (PDT) 已成为一种有效且微创的癌症治疗方法。在本研究中，我们研究了两种新型酞菁类化合物，四‑三乙氧基磺酰基取代锌酞菁 (ZnPc) 和二羟基‑2,9(10),16(17),23(24)‑四(4,7,10‑三氧杂十一烷‑1‑磺酰基)硅酞菁 (Pc32)，作为胆癌 (CC) 的光动力治疗光敏剂 (PS)。ZnPc 在 EGI-1 和 TFK-1 CC 细胞系中表现出明显的剂量依赖性和主要细胞质积累。Pc32 也在 CC 细胞中积累，但程度较轻。未经光激活，PS 没有表现出任何抗增殖或细胞毒性作用。光激活后，ZnPc 诱导活性氧 (ROS) 的形成和即刻光毒性，导致细胞增殖剂量依赖性下降，并诱导 EGI-1 和 TFK-1 细胞线粒体驱动的凋亡和细胞周期停滞。尽管光激活的 Pc32 也在这两种细胞系中诱导了 ROS 的形成，但与 ZnPc-PDT 诱导的 ROS 形成相比，程度较轻，并且仅在分化程度较低的 EGI-1 细胞中出现明显的抗增殖作用，而分化程度较高的 TFK-1 细胞在 Pc32-PDT 诱导后并未出现持续的生长抑制。使用绒毛尿囊膜 (CAM) 测定法对新型 PS 的抗血管生成效力进行了体内检查，结果显示，仅在用 ZnPc-PDT 诱导后，CAM 的血管生成发芽减少，未灌注区域增加，血管网络退化。该研究表明 ZnPc 作为一种新型 PS 具有明显的抗增殖和抗血管生成作用，是胆癌光动力治疗的有前途的 PS，值得进一步研究。
