Published online Dec 14, 2018. doi: 10.3748/wjg.v24.i46.5246
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
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.
Our findings will provide fundamental research for the clinical application of YLG-1 in pancreatic cancer therapy.
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.
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.
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.
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.
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.