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
ARTICLE HIGHLIGHTS
Research background

With the development of endoscopic ultrasonography (EUS) and EUS-guided fine needle aspiration (EUS-FNA), photodynamic therapy (PDT) has become a feasible treatment for advanced pancreatic neoplasms. The selection of an appropriate photosensitizer is of great importance in PDT. (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt (YLG-1) is hydrophilic chlorine derivative extracted from spirulina. It possesses characteristics including high purity, high water-solubility, high chemical stability, high phototoxicity, low dark toxicity as well as low price. Initially, YLG-1 was approved as a disinfection product for its great antimicrobial effect under illumination. However, the functions of YLG-1 in PDT are still poorly understood with no available publication.

Research motivation

Our findings will provide fundamental research for the clinical application of YLG-1 in pancreatic cancer therapy.

Research objectives

To explore the antitumor effects of YLG-1-induced PDT (YLG-1-PDT) on pancreatic cancer cells and its underlying mechanisms in vitro and in vivo.

Research methods

The human pancreatic cancer cell lines SW1990 and Panc-1 were used to detect the effects of YLG-1. CCK-8 assay, Bio-Tek Synergy H1, confocal microscopy, DCFH-DA, flow cytometry, and Western blot were exploited to detected the phototoxicity, cellular uptake, localization, reactive oxygen species (ROS) production, apoptosis and apoptosis-associated proteins (Bax, Bcl-2, and cleaved Caspase-3) expression, respectively. An in vivo imaging system (IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were used to assess the drug-delivered way of YLG-1 and pancreatic tumor growth in vivo.

Research results

YLG-1 was located in mitochondria and the appropriated incubation time was 6 h. Under 650 nm illumination, YLG-1 exhibited a potent phototoxicity on pancreatic cancer cells with a great generation of ROS in vitro. Besides, YLG-1-PDT induced pancreatic cancer cell apoptosis, upregulated Bax and cleaved Caspase-3 expression and decreased Bcl-2 expression. IVIS images indicated the optimal administration of YLG-1 was intratumoral (IT) injection and the best time to perform PDT was 2 h post IT injection. In accordance with the results in vitro, YLG-1-PDT potently inhibited the growth of pancreatic cancer cells in a mouse model. Notably, due to its small and highly soluble nature, YLG-1 lacked specific tumor-targeting accumulation and had better be applied by topical administration.

Research conclusions

YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are related with inducing ROS and promoting apoptosis. Hence, YLG-1-PDT might be a promising component of multimodality therapy of pancreatic neoplasms.

Research perspectives

Our results demonstrated that YLG-1-PDT had a potent antitumor effect on pancreatic cancer cells via inducing ROS and apoptosis. Since YLG-1 is lack of specific tumor-targeting accumulation, it might be suitable for superficial, luminal, and hypovascular tumors that need topical administration. Thus, YLG-1 is a promising photosensitizer in pancreatic cancer PDT in terms of its hypovascular character. In order to apply YLG-1 in more cancers, further studies should focus on modifying YLG-1 for target tumor accumulation.