经修饰的 5-氨基酮戊酸光动力疗法（M-PDT）通过靶向 PP2A/PP5 介导的 MAPK 信号通路抑制皮肤鳞状细胞癌细胞增殖。
Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) inhibits cutaneous squamous cell carcinoma cell proliferation via targeting PP2A/PP5-mediated MAPK signaling pathway.
机构信息
Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
出版信息
Int J Biochem Cell Biol. 2021 Aug;137:106036. doi: 10.1016/j.biocel.2021.106036. Epub 2021 Jul 2.
BACKGROUND
We previously demonstrated that M-PDT is painless and effective in precancerous skin diseases treatment. However, whether M-PDT is effective in cSCC and the underlying inhibitory mechanism remains enigmatic.
OBJECTIVE
We aims to unveil the effect of M-PDT on cSCC cell proliferation and the regulatory effect of M-PDT on MAPK signaling.
METHODS
The proliferation and migration of cSCC cells were revealed by CCK8 assay, tumor sphere formation assay and scratch assay respectively. The expression of MAPKs was examined by western blot. The activity of PP2A and PP5 was regulated by inhibitor and recombinant adenoviruses.
RESULTS
Here, we show that M-PDT inhibits cSCC cell proliferation by activating p-JNK, p-p38 and inhibiting p-Erk1/2, as well as activation of PP2A and inactivation of PP5. Furthermore, pharmacological inhibition of PP2A conferred resistance to M-PDT's suppression on p-Erk1/2 and attenuated inhibitory effects of M-PDT on cell proliferation whereas overexpression of wild-type PP2A showed the contrary results. Pharmacological inhibition of PP5 potentiated M-PDT's elevation on p-JNK and strengthened inhibitory effects of M-PDT on cell proliferation whereas overexpression of wild-type PP5 exhibited the contrary results.
CONCLUSION
Our findings indicate that M-PDT inhibits cSCC cell proliferation via targeting PP2A/PP5-mediated MAPK signaling pathway.
背景
我们之前证明了 M-PDT 在癌前皮肤病治疗中是无痛且有效的。然而，M-PDT 是否对 cSCC 有效以及其潜在的抑制机制仍然是个谜。
目的
我们旨在揭示 M-PDT 对 cSCC 细胞增殖的影响，以及 M-PDT 对 MAPK 信号通路的调节作用。
方法
通过 CCK8 检测、肿瘤球形成检测和划痕检测分别揭示 cSCC 细胞的增殖和迁移。通过 Western blot 检测 MAPKs 的表达。通过抑制剂和重组腺病毒调节 PP2A 和 PP5 的活性。
结果
在这里，我们表明 M-PDT 通过激活 p-JNK、p-p38 并抑制 p-Erk1/2，以及激活 PP2A 和失活 PP5，来抑制 cSCC 细胞的增殖。此外，PP2A 的药理学抑制赋予了细胞对 M-PDT 抑制 p-Erk1/2 的抵抗能力，并减弱了 M-PDT 对细胞增殖的抑制作用，而野生型 PP2A 的过表达则显示出相反的结果。PP5 的药理学抑制增强了 M-PDT 对 p-JNK 的升高，并加强了 M-PDT 对细胞增殖的抑制作用，而野生型 PP5 的过表达则显示出相反的结果。
结论
我们的研究结果表明，M-PDT 通过靶向 PP2A/PP5 介导的 MAPK 信号通路抑制 cSCC 细胞增殖。
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