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J Neurooncol. 2008 Feb;86(3):273-83. Epub 2007 Oct 11.

Lovastatin sensitized human glioblastoma cells to TRAIL-induced apoptosis.

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Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.


Synergy study with chemotherapeutic agents is a common in vitro strategy in the search for effective cancer therapy. For non-chemotherapeutic agents, efficacious synergistic effects are uncommon. Here, we have examined two non-chemotherapeutic agents for synergistic effects: lovastatin and Tumor Necrosis Factor (TNF)-related apoptosis-inducing ligand (TRAIL) for synergistic effects; on three human malignant glioblastoma cell lines, M059K, M59J, and A172. Cells treated with lovastatin plus TRAIL for 48 h showed 50% apoptotic cell death, whereas TRAIL alone (1,000 ng/ml) did not, suggesting that lovastatin sensitized the glioblastoma cells to TRAIL attack. Cell cycle analysis indicated that lovastatin increased G0-G1 arrest in these cells. Annexin V study demonstrated that apoptosis was the predominant mode of cell death. We conclude that the combination of lovastatin and TRAIL enhances apoptosis synergistically. Moreover, lovastatin sensitized glioblastoma cells to TRAIL, suggesting a new strategy to treat glioblastoma.

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