Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast cancer cells
Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast cancer cells
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DOI：
10.3892/or_00000087
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发表时间：
2008-10-01
期刊：
影响因子：
4.2
通讯作者：
Thomson, Jean
中科院分区：
文献类型：
--
作者：
Shennan, David B.;Thomson, Jean
已经表明，系统L（LAT 1/CD 98 hc）在癌细胞（包括乳腺肿瘤细胞）中上调，因此是抑制或限制肿瘤细胞生长的有希望的分子靶标。鉴于此，我们研究了BCH和其他系统L抑制剂对MCF-7、ZR-75-1和MDA-MB-231细胞生长的影响。用BCH处理细胞以剂量依赖方式显著抑制WST-1的代谢。同样，美法仑和D-亮氨酸抑制培养的乳腺癌细胞的生长，而MeAIB，系统A的抑制剂，没有效果。BCH和美法仑对细胞生长的影响是非加性的，这表明两种化合物作用于单个位点。结果表明，系统L是维持MCF-7、ZR-75-1和MDA-MB-231细胞生长所必需的，并支持LAT 1/CD 98 hc可能是抑制乳腺癌进展的合适靶点的观点。
It has been suggested that system L (LAT1/CD98hc) is up-regulated in cancer cells, including breast tumour cells, and is therefore a promising molecular target to inhibit or limit tumour cell growth. In view of this, we have examined the effect of BCH and other inhibitors of system L on the growth of MCF-7, ZR-75-1 and MDA-MB-231 cells. Treating cells with BCH markedly inhibited the metabolism of WST-1 in a dose-dependent fashion. Similarly, melphalan and D-leucine inhibited the growth of cultured breast cancer cells whereas MeAIB, an inhibitor of system A, was without effect. The effects of BCH and melphalan on cell growth were non-additive suggesting that both compounds were acting at a single locus. The results indicate that system L is required to maintain MCF-7, ZR-75-1 and MDA-MB-231 cell growth and support the notion that LAT1/CD98hc may be a suitable target to inhibit breast cancer progression.