Downregulation of Akt1 inhibits anchorage-independent cell growth and induces apoptosis in cancer cells

被引：43

作者：

Liu, XS ^{[1
]}

Shi, Y ^{[1
]}

Han, EKH ^{[1
]}

Chen, ZH ^{[1
]}

Rosenberg, SH ^{[1
]}

Giranda, VL ^{[1
]}

Luo, Y ^{[1
]}

Ng, SC ^{[1
]}

机构：

[1] Abbott Labs, Dept 47S, Div Pharmaceut Prod, Abbott Pk, IL 60064 USA

来源：

NEOPLASIA | 2001年 / 3卷 / 04期

关键词：

Akt1; apoptosis; antisense; oligonucleotide; cancer; combination treatment;

D O I：

10.1038/sj.neo.7900163

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The serine/threonine kinases, Akt1/PKB alpha, Akt2/PKB beta, and Akt3/PKB-gamma, 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.

引用

页码：278 / 286

页数：9

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