Elstad C A, Meadows G G
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman 99164-6510.
Anticancer Res. 1993 Mar-Apr;13(2):523-8.
We previously showed that restriction of tyrosine (Tyr) and phenylalanine (Phe) in vivo dramatically suppresses the metastatic phenotype of B16-BL6 (BL6) murine melanoma. Present results indicate a direct effect of Tyr and Phe restriction on the tumor in the absence of host selection pressures. Lung colonizing ability of BL6 is dramatically suppressed after one passage in vitro in media containing low levels of Tyr and Phe. This antimetastatic effect is immediate, stable for at least 5 in vitro passages in Tyr and Phe restricted media, and evident event after levels of Tyr and Phe are restored to normal. Heterogeneity for lung colonizing ability is suppressed, as evidence by fewer tumor colonies formed by clones following i.v. inoculation into mice fed normal diet. This suppression of BL6 metastatic phenotype is not due to differential clearance and retention in the lung or to decreased growth, but is specific for these two amino acids. As the mechanism(s) for the antitumor effects of Tyr and Phe restriction are detailed, the relevance of Tyr and Phe restriction as an early adjuvant to effective cancer treatment can be explored.
我们之前表明，体内限制酪氨酸（Tyr）和苯丙氨酸（Phe）能显著抑制B16-BL6（BL6）小鼠黑色素瘤的转移表型。目前的结果表明，在没有宿主选择压力的情况下，Tyr和Phe限制对肿瘤有直接影响。BL6在含有低水平Tyr和Phe的培养基中体外传代一次后，其肺定植能力显著受到抑制。这种抗转移作用是即时的，在Tyr和Phe限制培养基中至少体外传代5次仍稳定，并且在Tyr和Phe水平恢复正常后仍很明显。肺定植能力的异质性受到抑制，静脉注射接种到正常饮食小鼠体内的克隆形成的肿瘤集落减少即证明了这一点。BL6转移表型的这种抑制不是由于在肺中的差异清除和滞留，也不是由于生长减少，而是这两种氨基酸特有的。随着Tyr和Phe限制抗肿瘤作用机制的详细阐述，可以探索Tyr和Phe限制作为有效癌症治疗早期辅助手段的相关性。
