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Synergistic effects of photodynamic therapy with HPPH and gemcitabine in pancreatic cancer cell lines
Author(s) -
Sun Gang,
Anderson Marlys A.,
Gorospe Emmanuel C.,
Leggett Cadman L.,
Lutzke Lori S.,
Wong Kee Song Louis M.,
Levy Michael,
Wang Kenneth K.
Publication year - 2012
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.22073
Subject(s) - gemcitabine , photodynamic therapy , pancreatic cancer , cytotoxicity , programmed cell death , chemistry , cancer research , antimetabolite , cell culture , cancer , apoptosis , medicine , in vitro , biology , biochemistry , organic chemistry , genetics
Background and Objective Photodynamic therapy (PDT) is a potential treatment for pancreatic cancer. A second‐generation photosensitizer, 2‐[1‐hexyloxyethyl]‐2‐devinyl pyropheophorbide (HPPH) has a long wavelength absorption, high‐tumor selectivity, and shorter duration of skin photosensitivity. We investigated the efficacy of PDT with HPPH and gemcitabine in inducing cell death in multiple pancreatic cancer cell lines. Methods We used three pancreatic cancer cell lines (PANC‐1, MIA PaCa‐2, and BXPC‐3) incubated with HPPH concentration of 0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, and 0.5 µg/ml for 6 hours, followed by photoradiation at a light dose of 60 J/cm 2 . Afterwards, each cell line was treated with gemcitabine at concentrations of 0, 1, 10, and 100 µM and incubated for another 96 hours. Cell death was detected with SYTOX green staining. We also assessed the difference in cytotoxicity in adding gemcitabine before and after PDT. Results HPPH‐PDT can effectively induce cell death in all cell lines in a dose‐dependent manner, with a 100% of cell death at the 0.5 µg/ml HPPH concentration. In contrast, monotherapy with gemcitabine alone (100 µM) only achieved <45% cell death. Combining gemcitabine to HPPH‐PDT resulted in synergistic cytotoxic effect with 20–50% more cell death across all cell lines. There was no difference in cytotoxicity in adding gemcitabine before or after PDT. Conclusion This is the first study on HPPH‐PDT for pancreatic cancer. HPPH‐PDT‐induced cell death occurs in a dose‐dependent manner. HPPH‐PDT and gemcitabine have synergistic effects in inducing cell death in multiple pancreatic cancer cell lines. Lasers Surg. Med. 44: 755–761, 2012. © 2012 Wiley Periodicals, Inc.