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Endoplasmic reticulum stress-mediated autophagy contributes to 5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium-mediated photodynamic therapy via the PERK–eIF2α pathway

Authors Chen J, Huang JH, Wang Z, Song X, Chen Z, Zeng Q, Zhou X, Zuo Z, Zhao S, Chen X, Kang J

Received 22 January 2018

Accepted for publication 23 May 2018

Published 24 July 2018 Volume 2018:11 Pages 4315—4325

DOI https://doi.org/10.2147/OTT.S163366

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Justinn Cochran

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Jing Chen,1,* Jin-Hua Huang,1,* Zhen Wang,1,* Xiangzhi Song,2,* Zeyi Chen,1,* Qinghai Zeng,1,* Xiping Zhou,1,* Zhihong Zuo,1,* Shuang Zhao,3,* Xiang Chen,3,* Jian Kang1,*

1Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

*All authors contributed equally to this work

Introduction: 5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium (EtNBSe) is a novel synthetic bipolar photosensitizer with many promising applications. This study investigated the impact of EtNBSe-mediated photodynamic therapy (EtNBSe-PDT) on the autophagy and endoplasmic reticulum (ER) stress of squamous carcinoma cells (A-431 cells), as well as the related molecular mechanisms.
Methods: The potency of EtNBSe-PDT against squamous cell carcinoma was evaluated in BALB/c nude mice. Cell viability was evaluated using MTT. Western blotting and immunofluorescence were used to determine the expression levels of ER stress- and autophagy-related proteins.
Results: Both morphological and microscopic findings showed that the tumor on the xenograft mice exhibited an apparent reduction in volume and was replaced with fibrosis 20 days after EtNBSe-PDT. Additionally, in an in vitro study using A-431 cells, EtNBSe-PDT was found to inhibit A-431 cell survival in an EtNBSe concentration- and light dose- dependent manner, and to induce ER stress via the PERK-eIF2α signaling pathway. Additionally, EtNBSe-PDT could also induce autophagy of A-431 cells. Furthermore, the ER stress inhibitor 4-PBA and the eIF2α inhibitor salubrinal were found to inhibit the autophagy induced by EtNBSe-PDT.
Conclusion: This study demonstrated that the PERK-eIF2α signaling pathway was involved in the ER stress induced by EtNBSe-PDT. Meanwhile, the ER stress via the PERK-eIF2α pathway promoted the occurrence of autophagy in A-431 cells.

Keywords: photodynamic therapy, endoplasmic reticulum stress, squamous cell carcinoma, autophagy

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