Taxol is a powerful chemotherapeutic agent that binds to microtubules to prevent tumour cell division. However, a traditional high dose of
taxol may also induce apoptosis in normal cells. The anti-apoptotic molecule Bcl-2 is up-regulated in tumour cells to prevent apoptosis. We designed this study to determine whether use of a low dose of
taxol and anti-apoptotic Bcl-2 gene silencing would effectively induce apoptosis in human
glioblastoma U251MG cells and also inhibit invasion, angiogenesis and intracranial as well as subcutaneous tumour growth. We treated the cells with either 100 nM
taxol or transfected with a plasmid vector expressing Bcl-2
siRNA or both agents together for 72 h. Knockdown of Bcl-2 potentiated efficacy of
taxol for cell death. Fluorescence-activated cell sorting analysis, double immunofluorescent staining and TUNEL assay demonstrated apoptosis in about 70% of the cells
after treatment with the combination of
taxol and Bcl-2
siRNA. In vitro
Matrigel invasion assay demonstrated dramatic decrease in
glioblastoma cell invasion and in vivo angiogenesis assay showed complete inhibition of neovascularization in athymic nude mice
after treatment with the combination. Further, treatment with the combination of
taxol and Bcl-2
siRNA caused suppression of intracranial tumour growth and subcutaneous solid tumour development. In conclusion, our results indicate that the combination of
taxol and Bcl-2
siRNA effectively induces apoptosis and inhibits
glioblastoma cell invasion, angiogenesis and intracranial as well as subcutaneous tumour growth. Therefore, the combination of a low dose of
taxol and Bcl-2
siRNA is a promising therapeutic strategy for controlling the aggressive growth of human
glioblastoma.