Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 44, Issue 2, Pages 557-562Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2013.2205
Keywords
ZSTK474; phosphatidylinositol 3-kinase inhibitor; proteasome inhibitor; Velcade; glioblastoma multiforme
Categories
Funding
- Natural Science Foundation of China [81071788, 81272956]
- '985 project' of Sun Yat-sen University
- 'Team project' of Guangdong Provincial Department of Science and Technology [S2012030006287]
- Guangzhou Bureau of Science and Information Technology [2013J4500011, [2013]163]
- Key Laboratory of Guangdong Higher Education Institutes [KLB09001]
- National Institutes of Health [1U54CA143930-01, 5R01CA026038-32]
- A*STAR
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Proteasome inhibitors have been proven to be effective anticancer compounds in many tumor models, including glioblastoma multiforme (GBM). In this study, we found that the proteasome inhibitor Velcade (PS-341/bortezomib) caused GBM cell death while simultaneously activating the PI3K/Akt pathway. Therefore, we sought to investigate if the PI3K inhibitor ZSTK474 would enhance the effectiveness of Velcade in anticancer therapy. Two GBM cell lines were used to detect the effects of Velcade and ZSTK474 alone or in combination in vitro. The combination of Velcade and ZSTK474 synergistically inhibited the proliferation of GBM cell lines. Cell apoptosis was increased when exposed to Velcade and ZSTK474 in combination as shown by Annexin V analysis. Treatment with both drugs led to downregulation of the p-Akt, p-4EBP1 and p-mTOR proteins as determined by western blot analysis. The anticancer ability of Velcade for glioblastoma multiforme was, therefore, enhanced by combination with the PI3K pathway inhibitor ZSTK474 in glioblastoma multiforme.
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