title: Inhibition of Autophagy by Chloroquine Enhances the Antitumor Efficacy of Sorafenib in Glioblastoma.
abstract: Glioblastoma multiforme (GBM) is the most aggressive and common brain tumor in adults. Sorafenib, a multi-kinase inhibitor, has been shown to inhibit cell proliferation and induce apoptosis through inhibition of STAT3 signaling in glioblastoma cells and in intracranial gliomas. However, sorafenib also induces cell autophagy. Due to the dual roles of autophagy in tumor cell survival and death, the therapeutic effect of sorafenib on glioblastoma is uncertain. Here, we combined sorafenib treatment in GBM cells (U373 and LN229) and tumors with the autophagy inhibitor chloroquine. We found that blockage of autophagy further inhibited cell proliferation and migration and induced cell apoptosis in vitro and in vivo. These findings suggest the possibility of combination treatment with sorafenib and autophagy inhibitors for GBM.
authors.affiliation: Department of Neurosurgery, Nanjing Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Nanjing Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Kangjian
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Nanjing Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Surgery, School of Medicine, University of California, San Francisco, USA. yuyuandai@gmail.com.
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D002738:Chloroquine; D000077157:Sorafenib
keywords: Apoptosis; Autophagy; Glioblastoma; Sorafenib