BX795 Induces G2/M Cell Cycle Arrest in Oral Cancer Cells

• Main Authors: Yu-Chen Tsai, 蔡侑珍
• Other Authors: 翁靖如
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/40322669313310793788

碩士 === 中國醫藥大學 === 生物科技學系碩士班 === 100 === Research indicated that upstream signaling molecules (such as: Epidermal growth factor receptor, Row address strobe (Ras), Serum creatinine (Scr), or phosphoinositide 3-kinase (PI3K) of the signal pathway had overexpression in the tumor cells, and induced the activation of some signaling pathway, like the Mitogen-Activated protein kinase (MAPK) pathway or PDK1/Akt signaling pathway. These pathways lead to the activation of cancer cell proliferation. It has been reported that BX795, a PDK1 inhibitor blocked PDK1/Akt signaling in tumor cells and inhibited the growth of breast and prostate tumor cells in culture or induced apoptosis. Furthermore, BX795 is not only a PDK1 inhibitor, also inhibits Aurora B, IκB Kinase ε (IKKε), TANK-binding kinase 1 (TBK1) protein activity, decreasing effect of cancer cells growth and survival. In this study, the in vitro effects of BX795 were evaluated in HSC3, SCC2095, and SCC4 oral cancer cell lines, BX795 inhibited cell viability of HSC3, SCC2095, and SCC4 cells with IC50 of 2.0, 2.2, and 6.5 μM, respectively. It induced G2/M arrest in a dose dependent manner up to 2 μM. Mechanistic evidence indicates that BX795 downregulated the expression of TBK1、 Cyclin A、 Cyclin B1、 MPM2 and phosphorylation of Akt、 Cdc25C、 Cdc2, and upregulated the expression of p21. BX795 induced protein activation of procaspase 8, caspase-9 and PARP, and induced apoptosis. These above results indicated that BX795 induces cell cycle arrest and apoptosis in oral cancer cells.