N-methyl-d-aspartate (NMDA) receptors, which are widely present in the central nervous system, have also been found to be up-regulated in a variety of cancer cells and tumors and they can play active roles in cancer cell growth regulation. NMDA receptor antagonists have been found to affect cancer cell viability and interfere with tumor growth. Moreover, cancer cells also have been shown to have elevated levels of some d-amino acids. Two human skin cell lines: Hs 895.T skin cancer and Hs 895.Sk skin normal cells were investigated. They were derived from the same patient to provide tumor and normal counterparts for comparative studies. The expression of specific NMDA receptors was confirmed for the first time in both skin cell lines. Dizocilpine (MK-801) and memantine, NMDA receptor channel blockers, were found to inhibit the growth of human skin cells by reducing or stopping NMDA receptor activity. Addition of d-Ser, d-Ala, or d-Asp, however, significantly reversed the antiproliferative effect on the human skin cells triggered by MK-801 or memantine. Even more interesting was the finding that the specific intracellular composition of a few relatively uncommon amino acids was selectively elevated in skin cancer cells when exposed to MK-801. It appears that a few specific and upregulated d-amino acids can reverse the drug-induced antiproliferative effect in skin cancer cells via the reactivation of NMDA receptors. This study provides a possible innovative anticancer therapy by acting on the d-amino acid pathway in cancer cells either blocking or activating their regulatory enzymes.

N-甲基- d -天冬氨酸（NMDA）受体，其广泛存在于中枢神经系统中，也已发现被上调在各种癌细胞和肿瘤的并且它们可以在癌症细胞生长调节发挥积极作用。已经发现NMDA受体拮抗剂影响癌细胞的生存能力并干扰肿瘤的生长。此外，癌细胞也已经显示出具有一些水平升高d-氨基酸。研究了两种人类皮肤细胞系：Hs 895.T皮肤癌和Hs 895.Sk皮肤正常细胞。它们来自同一患者，以提供肿瘤和正常对照以进行比较研究。在两种皮肤细胞系中首次确认了特定NMDA受体的表达。已发现地佐西平（MK-801）和美金刚（NMDA受体通道阻滞剂）通过降低或停止NMDA受体活性来抑制人皮肤细胞的生长。d -Ser，d -Ala或d的加法-Asp可明显逆转MK-801或美金刚对人皮肤细胞的抗增殖作用。更加有趣的发现是，暴露于MK-801时，皮肤癌细胞中一些相对不常见的氨基酸的特定细胞内组成选择性升高。似乎一些特异性和上调的d-氨基酸可以通过NMDA受体的再激活来逆转药物诱导的皮肤癌细胞的抗增殖作用。这项研究通过作用于癌细胞中的d-氨基酸途径（阻断或激活其调节酶），提供了一种可能的创新抗癌治疗方法。