Department of Biochemistry and Biophysics, Vilnius University, Vilnius, Lithuania.
Photochem Photobiol. 2012 Mar-Apr;88(2):432-9. doi: 10.1111/j.1751-1097.2011.01062.x. Epub 2012 Jan 10.
Photodynamic therapy (PDT) of cancer induces oxidative stress, which intervenes in the expression of cytokines by tumor cells. The cytokines might have either a positive or a negative impact on tumor eradication. Here, we studied the expression of cytokines vascular endothelial growth factor (VEGF) and interleukin-1alpha (IL-1alpha) in the human epidermoid carcinoma A-431 cells following m-tetra(3-hydroxyphenyl)-chlorin (mTHPC)-mediated PDT in vitro and assessed the IL-1alpha effect on VEGF expression. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay revealed the enhanced production of VEGF and IL-1alpha both on mRNA and protein levels by mTHPC-loaded cells after light exposure. The silencing of IL1A by small interfering RNA resulted in decreased production of IL-1alpha and a reduced amount of VEGF. Furthermore, exogenous recombinant IL-1alpha stimulated the VEGF expression after PDT. Thus, in addition to the cytotoxic action on the A-431 cells, mTHPC-mediated PDT stimulated the production of VEGF and IL-1alpha, and IL-1alpha contributed to the VEGF overexpression. These data establish IL-1alpha as a possible target of combined cancer treatment.
光动力疗法（PDT）治疗癌症会引发氧化应激，从而干预肿瘤细胞中细胞因子的表达。这些细胞因子可能对肿瘤的清除有积极或消极的影响。在这里，我们研究了人表皮癌细胞 A-431 在体外接受 m-四（3-羟基苯基）-卟啉（mTHPC）介导的 PDT 后细胞因子血管内皮生长因子（VEGF）和白细胞介素-1α（IL-1α）的表达，并评估了 IL-1α 对 VEGF 表达的影响。定量聚合酶链反应和酶联免疫吸附试验显示，在 mTHPC 负载的细胞在暴露于光后，VEGF 和 IL-1α 在 mRNA 和蛋白质水平上的产生都增强了。通过小干扰 RNA 沉默 IL1A 导致 IL-1α 的产生减少和 VEGF 的量减少。此外，外源性重组 IL-1α 在 PDT 后刺激了 VEGF 的表达。因此，除了对 A-431 细胞的细胞毒性作用外，mTHPC 介导的 PDT 还刺激了 VEGF 和 IL-1α 的产生，而 IL-1α 有助于 VEGF 的过表达。这些数据确立了 IL-1α 作为联合癌症治疗的潜在靶点。
