Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2018; 24(46): 5246-5258
Published online Dec 14, 2018. doi: 10.3748/wjg.v24.i46.5246
Effect of photodynamic therapy with (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt on pancreatic cancer cells in vitro and in vivo
Yu-Jie Shen, Jia Cao, Fang Sun, Xiao-Lei Cai, Ming-Ming Li, Nan-Nan Zheng, Chun-Ying Qu, Yi Zhang, Feng Shen, Min Zhou, Ying-Wei Chen, Lei-Ming Xu
Yu-Jie Shen, Jia Cao, Fang Sun, Xiao-Lei Cai, Ming-Ming Li, Nan-Nan Zheng, Chun-Ying Qu, Yi Zhang, Feng Shen, Min Zhou, Ying-Wei Chen, Lei-Ming Xu, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Author contributions: Shen YJ and Cao J contributed equally to this work. Shen YJ and Cao J performed the majority of the experiments and wrote the paper; Sun F, Cai XL, Li MM, and Zheng NN analyzed the data; Qu CY, Zhang Y, Shen F, Zhou M, and Chen YW edited the manuscript; Xu LM designed and supervised the study; All authors have read and agreed with the final manuscript.
Supported by National Natural Science Foundation of China, No. 81472844.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (XHEC-NSFC-2018-036).
Institutional animal care and use committee statement: This study was reviewed and approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (XHEC-F-NSFC-2018-016).
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The ARRIVE guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Lei-Ming Xu, MD, PhD, Chief Doctor, Chief Physician, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China. xuleiming@xinhuamed.com.cn
Telephone: +86-21-25078999 Fax: +86-21-25078999
Received: September 25, 2018
Peer-review started: September 25, 2018
First decision: October 16, 2018
Revised: October 28, 2018
Accepted: November 13, 2018
Article in press: November 13, 2018
Published online: December 14, 2018
Abstract
AIM

To investigate the antitumor effects and underlying mechanisms of (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt (YLG-1)-induced photodynamic therapy (PDT) on pancreatic cancer in vitro and in vivo.

METHODS

YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species (ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system (IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.

RESULTS

YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine (NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral (IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.

CONCLUSION

YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.

Keywords: Photodynamic therapy, Pancreatic neoplasm, (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt, Antitumor effect

Core tip: Photodynamic therapy (PDT) has become a feasible treatment for advanced pancreatic neoplasms. Photosensitizers play a critical role in PDT. (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt (YLG-1) is a promising photosensitizer with high water solubility and phototoxicity. The functions of YLG-1-induced PDT (YLG-1-PDT) are still poorly understood. We found that YLG-1-PDT displayed great antitumor effects on pancreatic cancer cells in vitro and in vivo, the mechanisms of which involved inducing reactive oxygen species and promoting apoptosis. The optimal administration of YLG-1 towards pancreatic cancer is an intratumoral injection. Our study suggests that YLG-1 is a potential photosensitizer for pancreatic neoplasm PDT.