新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » BIOON报道 » IJC:阻断谷氨酰胺泵抑制黑色素瘤细胞生长

IJC:阻断谷氨酰胺泵抑制黑色素瘤细胞生长

来源:生物谷 2014-02-26 22:16

2014年2月27日讯 /生物谷BIOON/--悉尼大学科学家最新一项研究发现阻断谷氨酰胺泵能抑制黑色素瘤细胞的生长。去年,相关研究人员发现,阻断谷氨酰胺泵可以饿死前列腺癌。现在进一步的发现有助开辟一类新的药物,可以对一系列癌症包括黑色素瘤有抑制作用。

澳大利亚是世界上黑色素瘤发病率较高的国家,黑色素瘤是皮肤癌最致命的形式,在澳大利亚是第三大最常见的癌症。

不同于正常细胞,黑色素瘤和其他肿瘤细胞依赖于氨基酸谷氨酰胺而不是葡萄糖,来为分裂和生长提供能量。因而,为了推动癌细胞快速生长,癌细胞需要将谷氨酰胺“泵”入细胞内。

在Journal of Cancer杂志上发表的新的研究发现,黑色素细胞表面存在更多的谷氨酰胺泵,阻断这些泵将停止他们的成长。Jeff Holst博士等人已经证明,如果剥夺黑色素瘤必需营养物质,我们可以停止癌症生长。也即阻断谷氨酰胺进入肿瘤细胞,成功地减缓了肿瘤细胞的生长。

虽然如果及早发现,黑色素瘤会经常得到治愈,但黑色素瘤一旦已蔓延,仍是治疗最困难的癌症之一,因为它迅速产生耐药性。新研究提示专门针对并抑制谷氨酰胺泵或许将提供一个新治疗手段。(生物谷Bioon.com)

Targeting glutamine transport to suppress melanoma cell growth

Qian Wang,et al.

Amino acids, especially leucine and glutamine, are important for tumor cell growth, survival and metabolism. A range of different transporters deliver each specific amino acid into cells, some of which are increased in cancer. These amino acids consequently activate the mTORC1 pathway and drive cell cycle progression. The leucine transporter LAT1/4F2hc heterodimer assembles as part of a large complex with the glutamine transporter ASCT2 to transport amino acids. In this study, we show that the expression of LAT1 and ASCT2 is significantly increased in human melanoma samples and is present in both BRAFWT (C8161 and WM852) and BRAFV600E mutant (1205Lu and 451Lu) melanoma cell lines. While inhibition of LAT1 by BCH did not suppress melanoma cell growth, the ASCT2 inhibitor BenSer significantly reduced both leucine and glutamine transport in melanoma cells, leading to inhibition of mTORC1 signaling. Cell proliferation and cell cycle progression were significantly reduced in the presence of BenSer in melanoma cells in 2D and 3D cell culture. This included reduced expression of the cell cycle regulators CDK1 and UBE2C. The importance of ASCT2 expression in melanoma was confirmed by shRNA knockdown, which inhibited glutamine uptake, mTORC1 signaling and cell proliferation. Taken together, our study demonstrates that ASCT2-mediated glutamine transport is a potential therapeutic target for both BRAFWT and BRAFV600E melanoma.

 

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库