Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Department of Biophysics, Jagiellonian University, 31-007 Krakow, Poland.
Int J Mol Sci. 2024 May 23;25(11):5697. doi: 10.3390/ijms25115697.
Anti-tumor photodynamic therapy (PDT) is a unique modality that employs a photosensitizer (PS), PS-exciting light, and O to generate cytotoxic oxidants. For various reasons, not all malignant cells in any given tumor will succumb to a PDT challenge. Previous studies by the authors revealed that nitric oxide (NO) from inducible NO synthase (iNOS/NOS2) plays a key role in tumor cell resistance and also stimulation of migratory/invasive aggressiveness of surviving cells. iNOS was the only NOS isoform implicated in these effects. Significantly, NO from stress-upregulated iNOS was much more important in this regard than NO from preexisting enzymes. Greater NO-dependent resistance, migration, and invasion was observed with at least three different cancer cell lines, and this was attenuated by iNOS activity inhibitors, NO scavengers, or an iNOS transcriptional inhibitor. NO diffusing from PDT-targeted cells also stimulated migration/invasion potency of non-targeted bystander cells. Unless counteracted by appropriate measures, all these effects could seriously compromise clinical PDT efficacy. Here, we will review specific examples of these negative side effects of PDT and how they might be suppressed by adjuvants such as NO scavengers or inhibitors of iNOS activity or expression.
抗肿瘤光动力疗法（PDT）是一种独特的治疗方式，它利用光敏剂（PS）、PS 激发光和 O 来产生细胞毒性氧化剂。由于各种原因，任何给定肿瘤中的并非所有恶性细胞都会屈服于 PDT 挑战。作者之前的研究表明，来自诱导型一氧化氮合酶（iNOS/NOS2）的一氧化氮（NO）在肿瘤细胞耐药性以及存活细胞迁移/侵袭侵袭性的刺激中发挥关键作用。iNOS 是唯一与这些作用相关的 NOS 同工酶。重要的是，应激上调的 iNOS 产生的 NO 在这方面比预先存在的酶产生的 NO 更为重要。至少三种不同的癌细胞系观察到与 NO 依赖性耐药性、迁移和侵袭相关的作用增强，而通过 iNOS 活性抑制剂、NO 清除剂或 iNOS 转录抑制剂进行抑制。从 PDT 靶向细胞扩散的 NO 也刺激非靶向旁观者细胞的迁移/侵袭能力。除非采取适当的措施加以对抗，否则所有这些影响都可能严重影响临床 PDT 的疗效。在这里，我们将回顾 PDT 的这些负面副作用的具体实例，以及如何通过 NO 清除剂或 iNOS 活性或表达抑制剂等佐剂来抑制这些副作用。
