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
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.
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.
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.
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.
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.