重组蛋氨酸酶（rMETase）在原位小鼠模型中能有效靶向结直肠癌肝转移。
Colon-cancer liver metastasis is effectively targeted by recombinant methioninase (rMETase) in an orthotopic mouse model.
机构信息
AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
AntiCancer, Inc., San Diego, CA, USA.
出版信息
Tissue Cell. 2023 Aug;83:102125. doi: 10.1016/j.tice.2023.102125. Epub 2023 Jun 2.
BACKGROUND
Colorectal cancer liver metastasis (CCLM) is the most frequent cause of death of colorectal cancer. Development of novel new effective therapy is needed for CCLM patients to improve outcome. The aim of the present study was to investigate the efficacy of recombinant methioninase (rMETase) on a CCLM orthotopic mouse model of liver metastasis established using the human colon cancer cell line HT29 expressing red fluorescent protein (RFP).
MATERIALS AND METHODS
Orthotopic CCLM nude mouse models were randomized into two groups: control group (n = 6, PBS 200 µl, i.p., daily); rMETase group (n = 6, 100 units/200 µl, i.p., daily). Tumor volume was measured on day 0 and day 15. Body weight was measured twice a week. All mice were sacrificed on day 15.
RESULTS
rMETase significantly inhibited the increase of the liver metastasis as determined by RFP fluorescence area and intensity (p = 0.016 and 0.015, respectively). There was no significant difference of body weight between either group on any day.
CONCLUSIONS
The present study suggests that rMETase has future potential therapy for CCLM in the clinic.
背景
结直肠癌肝转移（CCLM）是结直肠癌患者死亡的最常见原因。需要为 CCLM 患者开发新的有效治疗方法，以改善预后。本研究旨在研究重组甲硫氨酸酶（rMETase）对表达红色荧光蛋白（RFP）的人结肠癌细胞系 HT29 建立的 CCLM 原位肝转移小鼠模型的疗效。
材料和方法
将原位 CCLM 裸鼠模型随机分为两组：对照组（n=6，PBS 200µl，腹腔内注射，每日一次）；rMETase 组（n=6，100 单位/200µl，腹腔内注射，每日一次）。在第 0 天和第 15 天测量肿瘤体积。每周测量两次体重。所有小鼠均在第 15 天处死。
结果
rMETase 显著抑制了 RFP 荧光面积和强度测定的肝转移增加（p=0.016 和 0.015）。两组在任何一天的体重均无显著差异。
结论
本研究表明，rMETase 具有临床治疗 CCLM 的潜在未来。
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