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Int. J. Mol. Sci. 2012, 13(7), 9142-9156; https://doi.org/10.3390/ijms13079142

TRAIL and Paclitaxel Synergize to Kill U87 Cells and U87-Derived Stem-Like Cells in Vitro

1
Department of Neurosurgery, First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China
2
Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
*
Author to whom correspondence should be addressed.
Received: 5 March 2012 / Revised: 11 July 2012 / Accepted: 11 July 2012 / Published: 20 July 2012
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

U87-derived stem-like cells (U87-SLCs) were cultured using serum-free stem cell media and identified by both biological behaviors and markers. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and paclitaxel (PX), in combination or alone, was used to treat U87-MG human glioma cells (U87 cells) or U87-SLCs. The results showed that TRAIL/PX cannot only synergistically inhibit U87 cells but also U87-SLCs. We observed a significantly higher apoptotic rate in U87 cells simultaneously treated with TRAIL/PX for 24 h compared to cells treated with either drug alone. Furthermore, there was a remarkably higher apoptosis rate in U87-SLCs induced by the TRAIL/PX combination compared with either drug alone. Unlike the simultaneous treatment in U87 cells, U87-SLCs were pretreated for 24 h with 1 μmol/L of PX followed by 1000 ng/mL of TRAIL. Protein assays revealed that TRAIL/PX synergy was related to DR4, cleaved caspase-8 and cleaved caspase-3 upregulation, whereas the mitochondrial pathway was not involved in TRAIL-induced apoptosis. The present study indicates that PX can sensitize U87 cells and U87-SLCs to TRAIL treatment through an extrinsic pathway of cell apoptosis. The combined treatment of TRAIL and PX may be a promising glioma chemotherapy because of its successful inhibition of U87-SLCs, which are hypothesized to influence chemotherapeutic outcomes of gliomas. View Full-Text
Keywords: glioma; glioma stem cells; U87-derived stem-like cells (U87-SLCs); tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL); paclitaxel; apoptosis glioma; glioma stem cells; U87-derived stem-like cells (U87-SLCs); tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL); paclitaxel; apoptosis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Qiu, B.; Sun, X.; Zhang, D.; Wang, Y.; Tao, J.; Ou, S. TRAIL and Paclitaxel Synergize to Kill U87 Cells and U87-Derived Stem-Like Cells in Vitro. Int. J. Mol. Sci. 2012, 13, 9142-9156.

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