combination of rgd compound and low-dose paclitaxel induces apoptosis in human glioblastoma cellsrgd复合和低剂量紫杉醇在人类胶质母细胞瘤细胞凋亡.pdfVIP

Combination of RGD Compound and Low-Dose Paclitaxel Induces Apoptosis in Human Glioblastoma Cells 1 1 2,3 2 1 Ming-Wei Chang , Jem-Mau Lo , Hsueh-Fen Juan , Hsin-Yi Chang , Chun-Yu Chuang * 1 Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, 2 Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan, 3 Department of Life Science, National Taiwan University, Taipei, Taiwan Abstract Background: Integrins are a family of transmembrane adhesion proteins that mediate cell adhesion and intracellular signaling. Integrin-avb3 is expressed on the surface of human glioblastoma cells, and can be further induced by chemical stress. The Arg-Gly-Asp (RGD) motif-containing peptides are specifically bound to integrin-avb3, and to inhibit neovasculature underlying competition to normal extracellular matrix proteins. This study employed two types of RGD peptides, cyclic RGD (c(RGDyK)) and bi-cyclic RGD (E[c(RGDyK)]2) peptide, to human glioblastoma U87MG cells with combination of low dose Paclitaxel (PTX) pre-treatment to augment therapeutic activity for RGD peptide-induced apoptosis. Principal Findings: Human glioblastoma U87MG cells were treated with RGD peptides in the absence or presence of initial exposure to low-dose 10 nM PTX. Results showed that integrin-avb3 expressing on the surface of U87MG cells was induced by 10 nM PTX pre-treatment for 12 hrs. Additionally, the U87MG cells pre-treated with PTX and followed by RGD peptides exhibited greater expression of caspases-3, -8 and -9 than those merely treated with single agent of PTX or RGD