Akt1亚型的基因缺失和药理学抑制可减弱膀胱癌细胞的增殖、运动性和侵袭能力。
Genetic deletion and pharmacological inhibition of Akt1 isoform attenuates bladder cancer cell proliferation, motility and invasion.
作者信息
Sabbineni Harika, Alwhaibi Abdulrahman, Goc Anna, Gao Fei, Pruitt Alanna, Somanath Payaningal R
机构信息
Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, United States.
Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, United States; Department of Medicine, Vascular Biology Center and Cancer Center, Georgia Regents University, Augusta, GA, United States.
出版信息
Eur J Pharmacol. 2015 Oct 5;764:208-214. doi: 10.1016/j.ejphar.2015.06.059. Epub 2015 Jul 3.
Isoform specific expression, intracellular localization and function of Akt in bladder cancer are not known. In the current study, we identified Akt1, followed by Akt2 and Akt3 as the predominant Akt isoform in human T24 and UM-UC-3 metastatic bladder cancer cells. Whereas Akt1 is localized at the membrane, cytoplasm and nucleus, Akt2 is solely cytoplasmic and Akt3 is mostly localized in the nucleus in T24 cells. ShRNA-mediated Akt1 knockdown resulted in impaired T24 cell survival, proliferation, colony formation, migration and microinvasion. Whereas pharmacological inhibition of Akt1 resulted in impaired T24 and UM-UC-3 cell motility, viability and proliferation, effect of pharmacological inhibition by Akt2 inhibitor was limited to proliferation in T24, but not UM-UC-3 cells. Our data provide important clues on the therapeutic benefits of targeting Akt1 for bladder cancer therapy.
Akt在膀胱癌中的亚型特异性表达、细胞内定位及功能尚不清楚。在本研究中，我们确定在人T24和UM-UC-3转移性膀胱癌细胞中，Akt1是主要的Akt亚型，其次是Akt2和Akt3。在T24细胞中，Akt1定位于细胞膜、细胞质和细胞核，Akt2仅定位于细胞质，Akt3主要定位于细胞核。短发夹RNA（shRNA）介导的Akt1敲低导致T24细胞存活、增殖、集落形成、迁移和微侵袭受损。而Akt1的药理学抑制导致T24和UM-UC-3细胞运动性、活力和增殖受损，Akt2抑制剂的药理学抑制作用仅限于T24细胞的增殖，对UM-UC-3细胞无此作用。我们的数据为靶向Akt1治疗膀胱癌的益处提供了重要线索。
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