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Photodynamic therapy for human hepatoma-cell–line tumors utilizing biliary excretion properties of indocyanine green

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Photodynamic therapy (PDT) has not been reported for human hepatoma, because cancer cells only weakly take up the photosensitizer. Indocyanine green (ICG) is a photosensitizer normally excreted into the bile, and bile excretion is impaired in human hepatomas. We examined whether human hepatoma cell lines preferentially take up the ICG and then assessed the effectiveness of PDT using ICG and near-infrared (NIR) laser.

Methods

HuH-7 and HepG2 human hepatoma cell lines were transplanted subcutaneously into mice. Developing HuH-7 and HepG2 tumors were confirmed that preferentially took up the ICG in 24 h after ICG was administered to mice via tail vein. The HuH-7 tumor showed a high tumor-to-background fluorescence intensity ratio, 255:1, whereas fluorescence intensity of HuH-7 is increased twofold compared to HepG2. HuH-7 cell transplanted mice were divided into three groups: ICG administration only (ICG+NIR−, n = 8), ICG and NIR laser exposure (ICG+NIR+, n = 12), and NIR laser exposure only (ICG−NIR+, n = 5).

Results

Mean tumor volume in the ICG+NIR− and ICG−NIR+ groups increased steadily. In contrast, mean tumor volume in the ICG+NIR+ group did not change between days 0 and 3. Mean tumor volume did not differ significantly between the ICG−NIR+ and ICG−NIR− groups, but was significantly different between the ICG+NIR+ group and both the ICG−NIR+ and ICG+NIR− groups (p < 0.01).

Conclusions

ICG is preferentially taken up by HuH-7 and HepG2 human hepatoma cell line tumors. The tumor-to-background ratio of HuH-7 tumors, in particular, was extremely high. PDT with NIR laser irradiation suppressed HuH-7 human hepatoma cell line tumor growth.

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Acknowledgments

This work was supported by grants 21791271 (Kaneko) and 23249067 (Kokudo) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and 2011 Tokyo Igakukai Medical Research Grants (Kaneko). We thank Dr. Yutaka Takazawa for helpful comments and suggestions regarding the pathology findings; Harukuni Tsuda for excellent technical assistance with the microscopic fluorescence evaluation; Yasuyuki Morishita for excellent technical assistance with histological preparation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Junichi Kaneko, Yoshinori Inagaki, Takeaki Ishizawa, Jianjun Gao, Wei Tang, Taku Aoki, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Yasuhiko Sugawara & Norihiro Kokudo

  2. Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

    Yoshinori Inagaki

  3. Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China

    Jianjun Gao

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  1. Junichi Kaneko
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  2. Yoshinori Inagaki
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  3. Takeaki Ishizawa
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  5. Wei Tang
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  10. Norihiro Kokudo
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Correspondence to Norihiro Kokudo.

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When the power density of the NIR light was increased from 0 to 4 mW/cm2, the entire mouse body (Immediately after ICG administration) and HuH-7 tumor (24 h after ICG administration) showed increased fluorescence intensity. When the NIR light was turned off, the fluorescence disappeared (MPG 10196 kb)

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Kaneko, J., Inagaki, Y., Ishizawa, T. et al. Photodynamic therapy for human hepatoma-cell–line tumors utilizing biliary excretion properties of indocyanine green. J Gastroenterol 49, 110–116 (2014). https://doi.org/10.1007/s00535-013-0775-4

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  • DOI: https://doi.org/10.1007/s00535-013-0775-4

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