title: Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.
abstract: Cullin 4A (Cul4A) has been observed to be overexpressed in various cancers. In this study, the role of Cul4A in the growth and chemosensitivity in lung cancer cells were studied. We showed that Cul4A is overexpressed in lung cancer cells and tissues. Knockdown of the Cul4A expression by shRNA in lung cancer cells resulted in decreased cellular proliferation and growth in lung cancer cells. Increased sensitivity to gemcitabine, a chemotherapy drug, was also noted in those Cul4A knockdown lung cancer cells. Moreover, increased expression of p21, transforming growth factor (TGF)-β inducible early gene-1 (TIEG1) and TGF beta-induced (TGFBI) was observed in lung cancer cells after Cul4A knockdown, which may be partially related to increased chemosensitivity to gemcitabine. G0/G1 cell cycle arrest was also noted after Cul4A knockdown. Notably, decreased tumour growth and increased chemosensitivity to gemcitabine were also noted after Cul4A knockdown in lung cancer xenograft nude mice models. In summary, our study showed that targeting Cul4A with RNAi or other techniques may provide a possible insight to the development of lung cancer therapy in the future.
authors.affiliation: Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.|Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan.
authors.forename: Ming-Szu
authors.initials: MS
authors.lastname: Hung
authors.affiliation: Department of Emergency Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.|Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan.
authors.forename: I-Chuan
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: You
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
authors.affiliation: Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Ya-Chin
authors.initials: YC
authors.lastname: Li
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Jr-Hau
authors.initials: JH
authors.lastname: Lung
authors.affiliation: Department of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shih-Tung
authors.initials: ST
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D044842:Cullin Proteins / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; C114234:CUL4A protein, human; D044842:Cullin Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Cul4A; chemotherapy; lung cancer; p21