Photodynamic therapy induces autophagy-mediated cell death in human colorectal cancer cells via activation of the ROS/JNK signaling pathway.
Photodynamic therapy induces autophagy-mediated cell death in human colorectal cancer cells via activation of the ROS/JNK signaling pathway.
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光动力疗法通过激活 ROS/JNK 信号通路诱导人结直肠癌细胞自噬介导的细胞死亡
DOI：
10.1038/s41419-020-03136-y
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发表时间：
2020-10-31
影响因子：
9
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Song C;Xu W;Wu H;Wang X;Gong Q;Liu C;Liu J;Zhou L
有证据表明m-THPC和维替普芬(VP)在光动力疗法(PDT)中是很有前途的增敏剂。此外，根据光敏剂(PS)和癌细胞类型的不同，自噬可以起到肿瘤抑制或肿瘤促进的作用。然而，在人结直肠癌(CRC)的体内外模型中，自噬在m-THPC和VP介导的PDT中的作用尚未见报道。在本研究中，m-THPC-PDT或VP-PDT表现出明显的光毒性，抑制了细胞的增殖，并诱导了结直肠癌细胞产生大量的活性氧(ROS)。通过免疫印迹、荧光图像分析和透射电子显微镜观察，我们发现ROS在细胞内诱导了广泛的自噬激活。此外，m-THPC-PDT或VP-PDT均可显著诱导大肠癌细胞凋亡。有趣的是，通过敲除ATG5或ATG7来抑制m-THPC-PDT诱导的自噬实质上抑制了结直肠癌细胞的凋亡。此外，m-THPC-PDT治疗可抑制HCT116皮下移植瘤的形成。同时，抗氧化剂通过抑制JNK信号通路，显著抑制PDT诱导的大肠癌细胞自噬和凋亡。总之，抑制自噬可以通过抑制ROS/JNK信号通路显著降低PDT介导的结肠癌细胞的抗癌效率。本研究为间THPC和VP在结直肠癌治疗中的应用提供了依据。
Evidence has shown that m-THPC and verteporfin (VP) are promising sensitizers in photodynamic therapy (PDT). In addition, autophagy can act as a tumor suppressor or a tumor promoter depending on the photosensitizer (PS) and the cancer cell type. However, the role of autophagy in m-THPC- and VP-mediated PDT in in vitro and in vivo models of human colorectal cancer (CRC) has not been reported. In this study, m-THPC-PDT or VP-PDT exhibited significant phototoxicity, inhibited proliferation, and induced the generation of large amounts of reactive oxygen species (ROS) in CRC cells. From immunoblotting, fluorescence image analysis, and transmission electron microscopy, we found extensive autophagic activation induced by ROS in cells. In addition, m-THPC-PDT or VP-PDT treatment significantly induced apoptosis in CRC cells. Interestingly, the inhibition of m-THPC-PDT-induced autophagy by knockdown of ATG5 or ATG7 substantially inhibited the apoptosis of CRC cells. Moreover, m-THPC-PDT treatment inhibited tumorigenesis of subcutaneous HCT116 xenografts. Meanwhile, antioxidant treatment markedly inhibited autophagy and apoptosis induced by PDT in CRC cells by inactivating JNK signaling. In conclusion, inhibition of autophagy can remarkably alleviate PDT-mediated anticancer efficiency in CRC cells via inactivation of the ROS/JNK signaling pathway. Our study provides evidence for the therapeutic application of m-THPC and VP in CRC.
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DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
影响因子：
--
作者：
Han, Xiaobo;Zhong, Zhaoyu;Yang, Liming
通讯作者：
Yang, Liming
影响因子：
2.1
作者：
Abdulrehman G;Xv K;Li Y;Kang L
通讯作者：
Kang L
影响因子：
--
作者：
Gheewala T;Skwor T;Munirathinam G
通讯作者：
Munirathinam G
影响因子：
2.6
作者：
Durbec, M.;Cosmidis, A.;Ceruse, P.
通讯作者：
Ceruse, P.