Gaowa Arong, Horibe Tomohisa, Kohno Masayuki, Harada Hiroshi, Hiraoka Masahiro, Kawakami Koji
Clin Exp Metastasis. 2016 Jan;33(1):87-95. doi: 10.1007/s10585-015-9760-z.
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.
在本研究中,我们调查了EGFR2R裂解杂合肽治疗结肠癌肝转移的疗效。通过WST-8法测定杂合肽对表达荧光素酶的人结肠癌(HCT-116-luc)细胞的细胞毒性活性。通过脾脏注射HCT-116-luc细胞建立肝转移实验小鼠模型。在细胞植入后第二天,以5mg/kg的剂量将杂合肽静脉注射到小鼠体内,每隔一天重复一次,共注射7次。用生理盐水处理的小鼠作为对照。通过IVIS成像系统监测肿瘤生长和治疗反应。结果表明,杂合肽对HCT-116-luc细胞具有强大的细胞毒性活性,与对照组相比,静脉注射杂合肽后肝转移明显减少。此外,Kaplan-Meier分析表明,经杂合肽治疗的小鼠生存期明显长于对照组。此外,肝脏组织的明场和离体成像显示,与对照组相比,经杂合肽治疗的小鼠肿瘤明显较少。这些结果表明,EGFR2R裂解杂合肽是肝内结直肠癌转移患者的一种潜在治疗选择。