Combination of RGD Compound and Low-Dose Paclitaxel Induces Apoptosis in Human Glioblastoma CellsReport as inadecuate




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Background

Integrins 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 cRGDyK and bi-cyclic RGD EcRGDyK2 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-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 EcRGDyK2 peptide induced U87MG programmed cell death. The increased expression of PTX-induced integrin-αvβ3 was correlated with the enhanced apoptosis in U87MG cells.

Conclusions

This 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.



Author: Ming-Wei Chang, Jem-Mau Lo, Hsueh-Fen Juan, Hsin-Yi Chang, Chun-Yu Chuang

Source: http://plos.srce.hr/



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