Department of Medicine, Laboratory of Biochemistry, University of Udine, P.le Kolbe 4, 33100, Udine, Italy.
Department of Medicine, Laboratory of Biochemistry, University of Udine, P.le Kolbe 4, 33100, Udine, Italy.
Nitric Oxide. 2022 Nov 1;128:25-36. doi: 10.1016/j.niox.2022.08.002. Epub 2022 Aug 12.
Photodynamic therapy (PDT) is a therapeutic modality based on the simultaneous action of three elements: photosensitizer, light and oxygen. This triad generates singlet oxygen and reactive oxygen species that can reduce the mass of a tumor. PDT is also able to stimulate iNOS, the enzyme that generates nitric oxide (NO). The role of NO in PDT-treated cancer cells has been investigated in several studies. They showed that low iNOS/NO levels stimulate signaling pathways that promote tumor survival, while high iNOS/NO levels arrest tumor growth. There is increasing evidence that ROS/RNS control both proliferation and migration of cells in the vicinity of PDT-treated tumor cells (so-called bystander cells). In this work, we addressed the question of how NO, which is generated by weak PDT, affects bystander cells. We used a conditioned medium: medium of PDT-treated tumor cells containing the stressors produced by the cells was added to untreated cells mimicking the neighboring bystander cells to investigate whether the conditioned medium affects cell proliferation. We found that low-level NO in prostate cancer cells affects the bystander tumor cells in a manner that depends on their malignancy grade.
光动力疗法（PDT）是一种基于三种元素的联合作用的治疗方式：光敏剂、光和氧。这三联体产生单线态氧和活性氧物质，从而可以减少肿瘤的质量。PDT 还能够刺激 iNOS，即产生一氧化氮（NO）的酶。在几项研究中已经研究了 NO 在 PDT 治疗的癌细胞中的作用。这些研究表明，低 iNOS/NO 水平会刺激促进肿瘤存活的信号通路，而高 iNOS/NO 水平会阻止肿瘤生长。越来越多的证据表明，ROS/RNS 控制 PDT 治疗肿瘤细胞附近的细胞的增殖和迁移（所谓的旁观者细胞）。在这项工作中，我们提出了一个问题，即由弱 PDT 产生的 NO 如何影响旁观者细胞。我们使用了一种条件培养基：添加来自 PDT 处理的肿瘤细胞的培养基，其中包含由细胞产生的应激物，以模拟未处理的细胞，从而研究条件培养基是否会影响细胞增殖。我们发现，低水平的 NO 会以依赖于其恶性程度的方式影响前列腺癌细胞中的旁观者肿瘤细胞。
