Potent anti-tumor effects of EGFR-targeted hybrid peptide on mice bearing liver metastases
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.
KeywordsLiver metastases Colorectal cancer Hybrid peptide Epidermal growth factor receptor Anti-tumor effect
Epidermal growth factor receptor
Vascular endothelial growth factor
Phosphate buffered saline
Hematoxylin and eosin
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.
Compliance with ethical standards
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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