title: G6PD downregulation triggered growth inhibition and induced apoptosis by regulating STAT3 signaling pathway in esophageal squamous cell carcinoma.
abstract: There is growing evidence that glucose-6-phosphate dehydrogenase (G6PD) is tightly associated with development and progression of many human tumors. However, its precise molecular mechanisms in esophageal squamous cell carcinoma (ESCC) remain unknown. In the current study, we found that G6PD messenger RNA (mRNA) and protein levels in ESCC cell lines (Eca109, EC1, and EC9706 cells) were significantly higher than that in normal esophageal epithelial cell line Het-1A (P < 0.05) and specific small interfering RNA (siRNA) against G6PD significantly reduced the levels of G6PD mRNA and protein in EC1 cells with highest G6PD levels (P < 0.05). Further investigation revealed that G6PD depletion contributed to the growth suppression in EC1 cells in vitro and EC1 cells xenografted nude mice in vivo, which was associated with the reduces of tumor weight and Ki-67 proliferation index, triggered cell cycle arrest at G0/G1 phase coupled with obvious decreases of cyclin D1 and CDK4 protein levels, and induced cell apoptosis accompanied by the increases of caspase-3 activity and Bax protein expression as well as the decrease of Bcl-2 protein expression in EC1 cells. More importantly, G6PD depletion significantly reduced the level of p-STAT3 protein but did not alter total STAT3 protein level. Taken altogether, our data presented herein suggest that G6PD may function as an important regulator in development and progression of ESCC by manipulating STAT3 signaling pathway and thus may be an underlying molecular target for therapy of the patients with ESCC.
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan, 450052, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.
authors.forename: Xiaqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Sciences, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, 450000, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan, 450052, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan, 450052, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan, 450052, People's Republic of China. fanruitai110@126.com.
authors.forename: Ruitai
authors.initials: R
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C000595707:BCL2 protein, human; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D005954:Glucosephosphate Dehydrogenase
keywords: Cell apoptosis; Cell cycle; Cell proliferation; Esophageal squamous cell carcinoma; Glucose-6-phosphate dehydrogenase; Signal transducer and activator of transcription 3