title: The multi-targeted tyrosine kinase inhibitor vandetanib plays a bifunctional role in non-small cell lung cancer cells.
abstract: Vandetanib, a multikinase inhibitor, is a target of drug treatments for non-small cell lung cancer (NSCLC). However, phase II and III clinical trials have not conclusively demonstrated the curative effects of vandetanib for NSCLC, and the reasons for this are unknown. In the present study, we use the NSCLC cell line Calu-6 as a model to determine the cellular and biological effects of vandetanib. Our results demonstrate that vandetanib impairs Calu-6 cell migration and invasion. We find that vandetanib can directly inhibit RET activity, which influences the Rho-JNK pathway. Overexpression of a constitutively active Rho GTPase antagonizes the inhibitory effects of vandetanib on Calu-6 cells invasion and JNK pathway activation. In addition, vandetanib induces autophagy by increasing the level of reactive oxygen species (ROS) in Calu-6 cells, and blockade of autophagy or ROS effectively enhances the cell death effect of vandetanib. In this study, we find vandetanib is of a double effect in some NSCLC cells, presenting new possibilities for the pharmacological treatment of NSCLC and introducing a novel role for vandetanib in treatment options.
authors.affiliation: Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai. 200127, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Shanghai Institute of Hematology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai. 200025, People's Republic of China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai. 200127, People's Republic of China.
authors.forename: Hanbing
authors.initials: H
authors.lastname: Zou
authors.affiliation: Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai. 200127, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Cai
authors.affiliation: Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai. 200127, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai. 200127, People's Republic of China.
authors.forename: Longmei
authors.initials: L
authors.lastname: Xu
authors.affiliation: 1] Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai. 200127, People's Republic of China [2] State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai. 200032, People's Republic of China.
authors.forename: Xianming
authors.initials: X
authors.lastname: Kong
authors.affiliation: 1] Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai. 200127, People's Republic of China [2] State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai. 200032, People's Republic of China.
authors.forename: Peifeng
authors.initials: P
authors.lastname: Liu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D020935:MAP Kinase Signaling System; D010880:Piperidines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D017382:Reactive Oxygen Species; D020741:rho GTP-Binding Proteins; C452423:vandetanib