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TRAIL and Paclitaxel Synergize to Kill U87 Cells and U87-Derived Stem-Like Cells in Vitro
Department of Neurosurgery, First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China
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; in revised form: 11 July 2012 / Accepted: 11 July 2012 / Published: 20 July 2012
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.
Keywords: glioma; glioma stem cells; U87-derived stem-like cells (U87-SLCs); tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL); paclitaxel; apoptosis
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MDPI and ACS Style
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.
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. International Journal of Molecular Sciences. 2012; 13(7):9142-9156.
Qiu, Bo; Sun, Xiyang; Zhang, Dongyong; Wang, Yong; Tao, Jun; Ou, Shaowu. 2012. "TRAIL and Paclitaxel Synergize to Kill U87 Cells and U87-Derived Stem-Like Cells in Vitro." Int. J. Mol. Sci. 13, no. 7: 9142-9156.