title: Lithium chloride suppresses colorectal cancer cell survival and proliferation through ROS/GSK-3β/NF-κB signaling pathway.
abstract: Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been regarded as a potential therapeutic target for multiple human cancers. In addition, oxidative stress is closely related to all aspects of cancer. We sought to determine the biological function of lithium, one kind of GSK-3β inhibitors, in the process of reactive oxygen species (ROS) production in colorectal cancer. In this study, we analyzed the cell apoptosis and proliferation by cell viability, EdU, and flow cytometry assays through administration of LiCl. We used polymerase chain reaction and Western blotting to establish the effect of GSK-3β inhibition on the nuclear factor-κB (NF-κB) pathway. Results showed administration of LiCl increased apoptosis and the level of ROS in colorectal cancer cells. Furthermore, the underlying mechanisms could be mediated by the reduction of NF-κB expression and NF-κB-mediated transcription. Taken together, our results demonstrated that therapeutic targeting of ROS/GSK-3β/NF-κB pathways may be an effective way for colorectal cancer intervention, although further preclinical and clinical testing are desirable.
authors.affiliation: Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
authors.forename: Kaixiong
authors.initials: K
authors.lastname: Tao
authors.affiliation: Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
authors.forename: Guobin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D005456:Fluorescent Dyes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D005456:Fluorescent Dyes; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000077022:Survivin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride