精氨酸琥珀酸合成酶作为乳腺癌个体化治疗新靶点的研究

摘要

氨基酸代谢在细胞生理学中有着举足轻重的作用,因为它参与了大量的细胞代谢和信号通路.精氨酸琥珀酸合成酶(ASS1)是尿素循环中的关键酶,在ASS1缺乏或表达较低的乳腺癌细胞中精氨酸缺乏,减少或降低精氨酸体内含量可以有效抑制肿瘤进展.实验结果表明,聚乙二醇化精氨酸脱亚胺酶(ADI-PEG20)促进精氨酸转变为瓜氨酸,从而降低精氨酸含量;同时mTOR抑制剂抑制CAD(氨甲酰磷酸合成酶2、天门冬氨酸转移酶和氨甲酰天冬氨酸脱水酶复合酶)的磷酸化,与ASS1竞争底物天冬氨酸,达到抑制乳腺癌细胞增殖生长的效果.提示ASS1可能成为抗癌新靶点.%Amino acid metabolism has a pivotal role in cellular physiology as it is being involved in numerous cellular metabolic and signaling pathways.Argininosuccinate synthetase 1 is a key enzyme in the urea cycle.ASS1 deficiency or low expression of breast cancer cells resulted in arginine deficiency,so reducing or decreasing the content of arginine can effectively inhibit tumor progression.Experimental results show that recombinant pegylated ADI(ADI-PEG20) promotes arginine into citrulline,thereby reducing the content of arginine.mTOR inhibitors can be used to inhibit the phosphorylation of CAD,and ASS1 competed with substrate aspartic acid to inhibit the growth and proliferation of breast cancer cells.ASS1 detection will become a new anti-cancer target.