Depletion of PI3K p85 alpha induces cell cycle arrest and apoptosis in colorectal cancer cells

作者：Sun Yan; Zhao Shiyi; Tian Hua; Xie Xiaoyun; Xiao Faman; Li Kang; Song Yugang^*

来源：Oncology Reports, 2009, 22(6): 1435-1441.

DOI：10.3892/or_00000585

• phosphatidylinositol 3-kinase p85 alpha
• RNA interference
• Forkhead box class O
• cell cycle
• apoptosis
• colorectal cancer

Colorectal cancer is one of the most common malignancies in the world. Overactivity of phosphatidylinositol 3-kinase (PI3K) is frequently detected in colorectal carcinoma. PI3K signaling plays a pivotal role in intracellular signal transduction pathways involved in cell growth, cellular transformation, and tumorigenesis. To specifically inhibit PI3K activity in colorectal cancer cells, we constructed a siRNA against the PI3K regulatory subunit p85 alpha and transfected it into LoVo and SW480 cells. In the present Study, treatment of colorectal cancer cells with PI3K p85 alpha-specific siRNA inhibited cell proliferation, induced G1 phase cell cycle arrest and sensitized colorectal cancer cells to 5-FU-induced apoptosis. Furthermore, depletion of PI3K p85a resulted in significant activation of three Forkhead box class O (FoxO) transcription factors, which inhibited the expression of cyclin D1, cdk4 and induced expression of p27/Kip1. Activation of FoxO transcription factors also increased the expression of FasL. Thus, our results indicate that siRNA-mediated gene silencing of PI3K p85 alpha may be a useful therapeutic strategy for colorectal carcinoma.

• 出版日期2009-12
• 单位南方医科大学