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J Cell Mol Med. 2016 Jul;20(7):1295-306. doi: 10.1111/jcmm.12811. Epub 2016 Mar 10.

Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.

Author information

1
Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
2
Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
3
Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan.
4
Department of Emergency Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
5
Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan.
6
Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
7
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
8
Department of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi, Taiwan.
9
Department of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
10
Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
11
Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

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.

KEYWORDS:

Cul4A; chemotherapy; lung cancer; p21

PMID:
26969027
PMCID:
PMC4929302
DOI:
10.1111/jcmm.12811
[Indexed for MEDLINE]
Free PMC Article

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