Hoffman Robert M, Hoshiya Yasunori, Guo Weiyan
AntiCancer, Inc., San Diego, CA, USA.
Department of Surgery, University of California, San Diego, CA, USA.
Methods Mol Biol. 2019;1866:75-81. doi: 10.1007/978-1-4939-8796-2_7.
Methionine (MET) dependence is the elevated requirement of cancer cells for MET. Cancer cells are arrested when MET is restricted in late S/G phase of the cell cycle. MET dependence may be the only known general metabolic defect in cancer. This chapter reviews the in vivo efficacy of dietary MET restriction (MR) to arrest human-cancer cell-line tumors and mouse tumors in nude mice. Human cancer xenografts in nude mice, when fed a MET-free diet, had greatly inhibited tumor growth. The body weight of mice on the MET-free diet was found to be maintainable by once-per-week administration of MET. These results suggested that MET dependence can be an important target for human cancer treatment. Yoshida sarcoma in nude mice on a MET-depleted diet regressed. MET depletion resulted in the extended survival of the tumor-bearing mice. These experiments are a prelude to further clinical studies of the efficacy of MR diets on cancer patients.
甲硫氨酸（MET）依赖性是癌细胞对甲硫氨酸的需求增加。当甲硫氨酸在细胞周期的S/G晚期受到限制时，癌细胞会停滞。MET依赖性可能是癌症中唯一已知的普遍代谢缺陷。本章综述了饮食中甲硫氨酸限制（MR）在裸鼠中抑制人癌细胞系肿瘤和小鼠肿瘤生长的体内疗效。给裸鼠体内的人癌异种移植瘤喂食无甲硫氨酸饮食后，肿瘤生长受到极大抑制。发现通过每周一次给予甲硫氨酸，无甲硫氨酸饮食小鼠的体重可得以维持。这些结果表明，MET依赖性可能是人类癌症治疗的一个重要靶点。食用甲硫氨酸缺乏饮食的裸鼠体内的吉田肉瘤消退。甲硫氨酸缺乏导致荷瘤小鼠存活期延长。这些实验是进一步对癌症患者进行MR饮食疗效临床研究的前奏。
