Synergistic effects of photodynamic therapy with HPPH and gemcitabine in pancreatic cancer cell lines

Authors

  • Gang Sun MD, PhD,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
    2. Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China
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  • Marlys A. Anderson BS,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
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  • Emmanuel C. Gorospe MD, MPH, CNSC,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
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  • Cadman L. Leggett MD,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
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  • Lori S. Lutzke CCRP,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
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  • Louis M. Wong Kee Song MD,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
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  • Michael Levy MD,

    1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
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  • Kenneth K. Wang MD

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
    • Russ and Kathy Van Cleve, Professor of Gastroenterology Research, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
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  • Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Abstract

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/cm2. 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.

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