Photodynamic therapy mediates immediate loss of cellular responsiveness to cytokines and growth factors.
Photodynamic therapy mediates immediate loss of cellular responsiveness to cytokines and growth factors.
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发表时间：
2003-07
期刊：
影响因子：
11.2
通讯作者：
Tak-Wah Wong;E. Tracy;A. Oseroff;H. Baumann
中科院分区：
文献类型：
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作者：
Tak-Wah Wong;E. Tracy;A. Oseroff;H. Baumann
光动力学疗法（PDT）是一种微创治疗方法，在恶性和非恶性疾病的治疗中具有越来越大的前景。大多数PDT研究都集中在如何增强光细胞毒性反应导致靶向肿瘤细胞凋亡和/或坏死的问题上。然而，存活的癌细胞以及正常宿主细胞的反应是促成结果的重要因素。很少有人知道这些细胞在治疗部位如何反应的炎症细胞因子和生长因子引起的PDT。为了回答这个问题，我们用破坏细胞膜和细胞膜的PDT治疗了几种上皮癌细胞系和正常上皮和基质细胞。在PDT后的不同时间点，用白细胞介素6类细胞因子或表皮生长因子（EGF）刺激细胞。细胞反应性通过信号蛋白的激活来确定。我们发现，在PDT反应的时间段内，正常和恶性细胞都失去了对细胞因子和生长因子的反应性，并呈PDT剂量依赖性。针对质膜或线粒体的光敏剂具有类似的效果。反应性的恢复需要48-72小时，并伴随着细胞增殖的恢复。虽然EGF反应的丧失可以通过EGF受体的立即降解来解释，但细胞因子反应的丧失仅部分地与细胞因子受体蛋白的减少相关。在HeLa细胞中也观察到PDT介导的Janus蛋白酪氨酸激酶-1的减少。我们的研究结果表明，PDT通过降低对已知有助于组织修复和免疫反应的因子的反应性来改变正常细胞和肿瘤细胞的调节能力。在预测PDT的结果时，必须考虑PDT的这种影响。
Photodynamic therapy (PDT) is a minimally invasive procedure with increasing promise in treatment of malignant and nonmalignant diseases. Most PDT studies have focused on issues of how to enhance the photocytotoxic reaction leading to apoptosis and/or necrosis of targeted tumor cells. However, the reactions of surviving cancer cells, as well as normal host cells, are important elements that contribute to the outcome. Little is known about how these cells at sites of treatment react to inflammatory cytokines and growth factors that are elicited by PDT. To answer this question, we treated several epithelial cancer cell lines and normal epithelial and stromal cells with membrane- and mitochondria-damaging PDT. At different time points after PDT, cells were stimulated with interleukin 6 class cytokines or epidermal growth factor (EGF). Cellular responsiveness was determined by the activation of signaling proteins. We found that within the time period of PDT reaction, both normal and malignant cells lost their responsiveness to the cytokines and growth factor in a PDT dose-dependent manner. Photosensitizers targeted to the plasma membrane or mitochondria had similar effects. The recovery of responsiveness required 48-72 h and was accompanied by resumption of cell proliferation. Although the loss of EGF response could be explained by the immediate degradation of EGF receptor, the loss of cytokine response was only, in part, correlated with a reduction in cytokine receptor proteins. A PDT-mediated reduction of Janus protein tyrosine kinase-1 was also observed in HeLa cells. Our results demonstrate that PDT alters the regulatory capability of normal and tumor cells by lowering the responsiveness to factors that are known to assist in tissue repair and immune response. This effect of PDT has to be considered when predicting outcome of PDT.