Uzdensky Anatoly, Kolpakova Elona, Juzeniene Asta, Juzenas Petras, Moan Johan
Institute for Cancer Research, 0310 Montebello, Oslo, Norway.
Biochim Biophys Acta. 2005 Feb 11;1722(1):43-50. doi: 10.1016/j.bbagen.2004.11.011. Epub 2004 Dec 15.
5-Aminolevulinic acid (ALA), a precursor of the endogenous photosensitizer protoporphyrin IX, is used in the photodynamic therapy (PDT) of cancer. Sub-lethal ALA-PDT (1-min irradiation with 370-450 nm blue light, 0.6 mW/cm(2) after 2-h incubation with 1 mM ALA) has been earlier shown to change cell morphology and to inhibit both trypsin-induced detachment of cultured cancer cells from the plastic substrata and cell attachment to the bottom of the plastic well plates. In the present study, we found that such treatment of human adenocarcinoma WiDr cells grown in dense colonies stimulated the formation of actin cortex between cells in the colonies and increased the number of actin stress fibres in some, but not in all, cells. However, ALA-PDT did not change the microtubular cytoskeleton in these cells. A similar treatment of glioblastoma D54Mg cells, which grow separately and communicate by protrusions, caused loss of fibrillar actin structures in growth cones, retraction of protrusions, and surface blebbing in some cells. The application of the cytoskeleton inhibitors cytochalasin D, colchicine or taxol showed that the inhibition of trypsin-induced detachment of photosensitized WiDr cells was related to ALA-PDT-induced changes in actin and microtubular cytoskeleton. Some signal transduction processes are suggested to be involved in ALA-PDT-induced changes in cytoskeleton, cell shape, and adhesion.
5-氨基酮戊酸(ALA)是内源性光敏剂原卟啉IX的前体,用于癌症的光动力疗法(PDT)。亚致死剂量的ALA-PDT(用1 mM ALA孵育2小时后,用370 - 450 nm蓝光照射1分钟,0.6 mW/cm²)先前已被证明会改变细胞形态,并抑制胰蛋白酶诱导的培养癌细胞从塑料基质上脱离以及细胞附着于塑料孔板底部。在本研究中,我们发现对密集集落生长的人腺癌WiDr细胞进行这种处理会刺激集落中细胞间肌动蛋白皮层的形成,并增加部分(但并非全部)细胞中肌动蛋白应力纤维的数量。然而,ALA-PDT并未改变这些细胞中的微管细胞骨架。对单独生长并通过突起相互连接的胶质母细胞瘤D54Mg细胞进行类似处理,导致生长锥中丝状肌动蛋白结构丧失、突起回缩以及部分细胞出现表面气泡现象。应用细胞骨架抑制剂细胞松弛素D、秋水仙碱或紫杉醇表明,抑制胰蛋白酶诱导的光敏化WiDr细胞脱离与ALA-PDT诱导的肌动蛋白和微管细胞骨架变化有关。一些信号转导过程被认为参与了ALA-PDT诱导的细胞骨架、细胞形状和黏附的变化。