Department of Pathology, Wrocław Medical University, 50-367 Wrocław, Poland.
Department of Medical Biochemistry, Wrocław Medical University, 50-367 Wrocław, Poland.
Photodiagnosis Photodyn Ther. 2014 Mar;11(1):27-33. doi: 10.1016/j.pdpdt.2013.11.002. Epub 2013 Nov 23.
There are proteins, responsible for many basic cell functions (transmission of extracellular signals to cytoplasm or nucleus, cell growth, proliferation, migration, survival), which are activated and overexpressed in response to acute oxidative stress, especially tyrosine kinases. The oxidative stress-associated Src activator/Homo sapiens chromosome 9 open reading frame 10 protein (Ossa/C9orf10) protects cancer cells from oxidative stress-induced apoptosis by Src family kinases activation.
In this study precursor of protoporphyrin IX, 5-aminolevulinic acid and its encapsulated form were used in treating MCF-7 human breast cancer cells. After light illumination, cells were collected at different time points and used for evaluation (immunocytochemistry, Western blot analysis) of expression of above proteins, c-Src and Ossa.
Our results showed that 5-aminolevulinic acid-mediated photodynamic therapy caused decrease of c-Src expression at 7h after irradiation. The strongest expression was observed at 24h after treatment. Encapsulated form of 5-aminolevulinic acid in terms of PDT caused similar changes of expression of c-Src protein. Furthermore, we observed strong Ossa expression at 7h after treatment in comparison to very low expression at time points 0, 18 and 24h.
We would like to emphasize that our results showed high expression of Ossa at early time interval after PDT, which was accompanied by a low expression of c-Src kinase, what could protect cancer cells from PDT through activation of c-Src in response to oxidative stress.
有一些蛋白质负责许多基本的细胞功能（将细胞外信号传递到细胞质或细胞核、细胞生长、增殖、迁移、存活），它们会在急性氧化应激下被激活和过度表达，尤其是酪氨酸激酶。与氧化应激相关的Src 激活剂/人类 9 号染色体开放阅读框 10 蛋白（Ossa/C9orf10）通过激活 Src 家族激酶来保护癌细胞免受氧化应激诱导的细胞凋亡。
在这项研究中，我们使用原卟啉 IX 的前体、5-氨基酮戊酸及其包封形式来治疗 MCF-7 人乳腺癌细胞。在光照后，在不同时间点收集细胞，用于评估上述蛋白质、c-Src 和 Ossa 的表达（免疫细胞化学、Western blot 分析）。
我们的结果表明，5-氨基酮戊酸介导的光动力疗法在照射后 7 小时导致 c-Src 表达减少。最强的表达发生在治疗后 24 小时。5-氨基酮戊酸的包封形式在 PDT 方面导致 c-Src 蛋白表达的类似变化。此外，我们观察到治疗后 7 小时 Ossa 的表达很强，而在 0、18 和 24 小时的时间点表达非常低。
我们想强调的是，我们的结果表明，在 PDT 后早期时间间隔，Ossa 的表达很高，同时 c-Src 激酶的表达很低，这可以通过激活 c-Src 来保护癌细胞免受 PDT 引起的氧化应激。
