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Potent anti-tumor effects of EGFR-targeted hybrid peptide on mice bearing liver metastases

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Abstract

In this study, we investigated the therapeutic efficacy of EGFR2R-lytic hybrid peptide for the treatment of liver metastasis from colon carcinoma. The cytotoxic activity of the hybrid peptide against luciferase-expressing human colon cancer (HCT-116-luc) cells was determined by the WST-8 assay. The experimental mouse model of liver metastases was generated by splenic injection of HCT-116-luc cells. The hybrid peptide was intravenously injected into mice the day after cell implantation at a dose of 5 mg/kg and this was repeated on alternate days for a total of 7 doses. Saline-treated mice were used as controls. Tumor growth and therapeutic responses were monitored by an IVIS imaging system. It was shown that the hybrid peptide exhibited potent cytotoxic activity against HCT-116-luc cells and the liver metastases were significantly reduced after intravenous injections of hybrid peptide compared with controls. Furthermore, Kaplan–Meier analysis showed that hybrid peptide-treated mice had significantly longer survival than controls. In addition, bright-field and ex vivo imaging of liver tissue revealed that mice treated with the hybrid peptide had significantly fewer tumors compared with controls. These results demonstrated that the EGFR2R-lytic hybrid peptide is a potential treatment option for patients with colorectal cancer metastases in the liver.

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Abbreviations

EGFR:

Epidermal growth factor receptor

VEGF:

Vascular endothelial growth factor

PBS:

Phosphate buffered saline

Luc:

Luciferase

H&E:

Hematoxylin and eosin

AST:

Aspartate transaminase

ALT:

Alanine aminotransferase

LDH:

Lactate dehydrogenase

TKI:

Tyrosine kinase

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Acknowledgments

We thank Mitsuko Tachi, Yoshie Masuda and Nanako Okushima (Department of Pharmacoepidemiology, Kyoto University) for their technical assistance in cell culture and animal studies. This study was supported by Grants-in-Aid for Young Scientist (A) (Grant No. 23680089) from the Japan Society for the Promotion of Science. This study was also supported in part by a collaboration research fund from Olympus Corporation.

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Authors and Affiliations

  1. Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan

    Arong Gaowa, Tomohisa Horibe, Masayuki Kohno & Koji Kawakami

  2. Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shyogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Hiroshi Harada & Masahiro Hiraoka

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  1. Arong Gaowa
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  2. Tomohisa Horibe
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  3. Masayuki Kohno
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  4. Hiroshi Harada
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  5. Masahiro Hiraoka
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  6. Koji Kawakami
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Correspondence to Koji Kawakami.

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Conflict of interest

Koji Kawakami serves as a scientific advisor to Olympus Corporation. None of the other authors have any potential competing interest.

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Gaowa, A., Horibe, T., Kohno, M. et al. Potent anti-tumor effects of EGFR-targeted hybrid peptide on mice bearing liver metastases. Clin Exp Metastasis 33, 87–95 (2016). https://doi.org/10.1007/s10585-015-9760-z

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  • DOI: https://doi.org/10.1007/s10585-015-9760-z

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