Abstract
BackgroundIntegrins are a family of transmembrane adhesion proteins that mediate cell adhesion and intracellular signaling. Integrin-αvβ3 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-αvβ3, 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 FindingsHuman 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-αvβ3 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 peptide. Furthermore, the caspase-3, -8 and -9 inhibitor presented significant protection against E[c(RGDyK)]2 peptide induced U87MG programmed cell death. The increased expression of PTX-induced integrin-αvβ3 was correlated with the enhanced apoptosis in U87MG cells.ConclusionsThis study provides a novel concept of targeting integrin-αvβ3 with RGD peptides in combination with low-dose PTX pre-treatment to improve efficiency in human glioblastoma treatment.
Highlights
Glioblastoma multiforme (GBM) is a common type of human brain tumor composed of poorly differentiated astrocytes [1]
This study provides a novel concept of targeting integrin-avb3 with RGD peptides in combination with lowdose PTX pre-treatment to improve efficiency in human glioblastoma treatment
This study investigates the apoptotic potential and the gene network of the caspase cascade in U87MG cells undergoing RGD peptides specific-targeting to integrin-avb3 that is enhanced by low-dose PTX treatment
Summary
Glioblastoma multiforme (GBM) is a common type of human brain tumor composed of poorly differentiated astrocytes [1]. The progression of tumor invasiveness and metastasis is positively correlated with the expression levels of integrin-avb in human prostate cancer LNCaP cells [12]. When antagonized by RGD peptides, the integrin-avb receptor protein has the capability to program cell death through cell apoptosis or neovasculacture inhibition in human glioblastoma (10 mM RGD peptides), lung fibroblasts (0.8 mM) and breast carcinoma MCF-7 cells (1 mM) [1,13,14,15]. The RGD pentapeptide Cilengitide (EMD 121974, Merck), an antagonist of integrin-avb, is currently used to treat tumors by inhibiting angiogenesis in clinical phase 3 testing for GBM, and phase 1, 2 trials for metastatic squamous cell carcinoma and advanced non-small cell lung cancer [16,17,18]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
