title: Dysregulation of the PI3K/Akt signaling pathway affects cell cycle and apoptosis of side population cells in nasopharyngeal carcinoma.
abstract: Increasing evidence has suggested that certain types of cancer possess their own stem-like cells, and that one subset of these cells, termed the side population (SP), may have an important role in tumorigenesis and cancer therapy. However, the molecular mechanisms underlying the modulation of SP cells in nasopharyngeal carcinoma (NPC) have remained elusive. In the present study, it was hypothesized that dysregulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway may influence SP and non-SP (NSP) phenotype. SP cells from the HK-1 NPC cell line were identified, and cancer stem cell markers were found to be highly expressed in SP cells compared with that of NSP cells. Freshly sorted SP cells demonstrated a significant increase in the proportion of cells in G0/G1 phase, while the majority of NSP cells were in the proliferative phase. Following 48 h of culture subsequent to cell sorting, the differences in cell cycle distribution between the SP and NSP cells converged. In addition, the apoptotic ratio of NSP cells was higher than that of SP cells at 24 h following sorting, but had no significant differences 48 h following sorting. To elucidate the potential mechanism mediating the cell cycle and apoptosis in SP cells, the expression levels of key molecules in the PI3K/Akt signaling pathway were evaluated. PI3K and Akt were upregulated, while 14-3-3σ protein was downregulated in SP cells when freshly sorted (0 h). However, there was no significant difference in the expression of these molecules between SP and NSP cells following 48 h of culture. These results suggested that dysregulation of the PI3K/Akt signaling pathway may be associated with the cell cycle and apoptosis of SP cells in NPC. However, further investigation is required to elucidate the detailed mechanisms underlying these effects.
authors.affiliation: Medical Experimental Center, Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China ; Molecular Genetics Laboratory, Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Changsha, Hunan 410078, P.R. China ; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Danwei
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Medical Experimental Center, Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China ; Molecular Genetics Laboratory, Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Changsha, Hunan 410078, P.R. China ; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Guangchao
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Medical Experimental Center, Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China ; Molecular Genetics Laboratory, Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Changsha, Hunan 410078, P.R. China ; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Liao
authors.affiliation: Medical Experimental Center, Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China ; Molecular Genetics Laboratory, Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Changsha, Hunan 410078, P.R. China ; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Pathology, Basic School of Medicine, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Gengqiu
authors.initials: G
authors.lastname: Luo
authors.affiliation: Medical Experimental Center, Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China ; Molecular Genetics Laboratory, Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Changsha, Hunan 410078, P.R. China ; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Junyu
authors.initials: J
authors.lastname: He
authors.affiliation: Medical Experimental Center, Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China ; Molecular Genetics Laboratory, Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Changsha, Hunan 410078, P.R. China ; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Pei
authors.affiliation: Medical Experimental Center, Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China ; Molecular Genetics Laboratory, Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Changsha, Hunan 410078, P.R. China ; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: Medical Experimental Center, Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China ; Molecular Genetics Laboratory, Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Changsha, Hunan 410078, P.R. China ; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
keywords: apoptosis; cell cycle; nasopharyngeal carcinoma; side population cells; signal pathway