Akt1的下调抑制癌细胞的非锚定依赖性细胞生长并诱导其凋亡。
Downregulation of Akt1 inhibits anchorage-independent cell growth and induces apoptosis in cancer cells.
作者信息
Liu X, Shi Y, Han E K, Chen Z, Rosenberg S H, Giranda V L, Luo Y, Ng S C
机构信息
Cancer Research, Pharmaceutical Product Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
出版信息
Neoplasia. 2001 Jul-Aug;3(4):278-86. doi: 10.1038/sj.neo.7900163.
The serine/threonine kinases, Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma, play a critical role in preventing cancer cells from undergoing apoptosis. However, the function of individual Akt isoforms in the tumorigenicity of cancer cells is still not well defined. In the current study, we used an Akt1 antisense oligonucleotide (AS) to specifically downregulate Akt1 protein in both cancer and normal cells. Our data indicate that Akt1 AS treatment inhibits the ability of MiaPaCa-2, H460, HCT-15, and HT1080 cells to grow in soft agar. The treatment also induces apoptosis in these cancer cells as demonstrated by FACS analysis and a caspase activity assay. Conversely, Akt1 AS treatment has little effect on the cell growth and survival of normal human cells including normal human fibroblast (NHF), fibroblast from muscle (FBM), and mammary gland epithelial 184B5 cells. In addition, Akt1 AS specifically sensitizes cancer cells to typical chemotherapeutic agents. Thus, Akt1 is indispensable for maintaining the tumorigenicity of cancer cells. Inhibition of Akt1 may provide a powerful sensitization agent for chemotherapy specifically in cancer cells.
丝氨酸/苏氨酸激酶Akt1/PKBα、Akt2/PKBβ和Akt3/PKBγ在防止癌细胞凋亡方面发挥着关键作用。然而，单个Akt亚型在癌细胞致瘤性中的功能仍未明确界定。在本研究中，我们使用Akt1反义寡核苷酸（AS）特异性下调癌细胞和正常细胞中的Akt1蛋白。我们的数据表明，Akt1 AS处理可抑制MiaPaCa-2、H460、HCT-15和HT1080细胞在软琼脂中生长的能力。如流式细胞术分析和半胱天冬酶活性测定所示，该处理还可诱导这些癌细胞凋亡。相反，Akt1 AS处理对包括正常人成纤维细胞（NHF）、肌肉来源的成纤维细胞（FBM）和乳腺上皮184B5细胞在内的正常人细胞的生长和存活影响很小。此外，Akt1 AS可使癌细胞对典型化疗药物敏感。因此，Akt1对于维持癌细胞的致瘤性不可或缺。抑制Akt1可能为癌症细胞的化疗提供一种强大的增敏剂。
Zotero 插件