口服重组蛋氨酸酶产生菌可抑制同基因小鼠模型结直肠癌的生长。
Oral Installation of Recombinant Methioninase-producing into the Microbiome Inhibits Colon-cancer Growth in a Syngeneic Mouse Model.
机构信息
AntiCancer Inc., San Diego, CA, U.S.A.
Department of Surgery, University of California, San Diego, CA, U.S.A.
出版信息
Cancer Genomics Proteomics. 2022 Nov-Dec;19(6):683-691. doi: 10.21873/cgp.20351.
BACKGROUND/AIM: All cancer types so far tested are methionine-addicted. Targeting the methionine addiction of cancer with recombinant methioninase (rMETase) has shown great progress in vitro, in mouse models, and in the clinic. However, administration of rMETase requires multiple doses per day. In the present study, we determined if rMETase-producing Escherichia coli JM109 (E. coli JM109-rMETase) might be an effective anticancer agent when installed into the microbiome.
MATERIALS AND METHODS
E. coli JM109-rMETase was administered to a syngeneic model of MC38 colon cancer growing subcutaneously in C57BL/6 mice. JM109-rMETase was administered orally by gavage to the mice twice per day. Tumor size was measured with calipers.
RESULTS
The administration of E. coli JM109-rMETase twice a day significantly inhibited MC38 colon-cancer growth. E. coli JM109-rMETase was found in the stool of treated mice, indicating it had entered the microbiome.
CONCLUSION
The present study indicates the potential of microbiome-based treatment of cancer targeting methionine addiction.
背景/目的：迄今为止测试的所有癌症类型都依赖于蛋氨酸。用重组蛋氨酸酶（rMETase）靶向癌症的蛋氨酸成瘾，在体外、小鼠模型和临床中都取得了很大进展。然而，rMETase 的给药需要每天多次。在本研究中，我们确定如果将产生 rMETase 的大肠杆菌 JM109（E. coli JM109-rMETase）植入微生物组中，是否可能成为一种有效的抗癌药物。
材料和方法
将 rMETase 产生的大肠杆菌 JM109（E. coli JM109-rMETase）施用于皮下生长 MC38 结肠癌细胞的同基因模型的 C57BL/6 小鼠中。通过灌胃每天两次向小鼠口服给予 JM109-rMETase。用卡尺测量肿瘤大小。
结果
每天两次给予大肠杆菌 JM109-rMETase 可显著抑制 MC38 结肠癌细胞的生长。在接受治疗的小鼠的粪便中发现了大肠杆菌 JM109-rMETase，表明它已进入微生物组。
结论
本研究表明，针对蛋氨酸成瘾的基于微生物组的癌症治疗具有潜力。
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