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

作者：Gaowa Arong; Horibe Tomohisa; Kohno Masayuki; Harada Hiroshi; Hiraoka Masahiro; Kawakami Koji^*

来源：Clinical & Experimental Metastasis, 2016, 33(1): 87-95.

DOI：10.1007/s10585-015-9760-z

• Liver metastases
• Colorectal cancer
• Hybrid peptide
• Epidermal growth factor receptor
• Anti-tumor effect

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.

• 出版日期2016-1