title: TRAIL and paclitaxel synergize to kill U87 cells and U87-derived stem-like cells in vitro.
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.
authors.affiliation: Department of Neurosurgery, First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qiu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Xiyang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China.
authors.forename: Dongyong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Neurosurgery, First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China.
authors.forename: Shaowu
authors.initials: S
authors.lastname: Ou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000819:agonists / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D053181:Caspase 8 / Q000096:biosynthesis; D002460:Cell Line; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000819:agonists / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D017239:Paclitaxel