Dysregulation of the PI3K/Akt signaling pathway affects cell cycle and apoptosis of side population cells in nasopharyngeal carcinoma.
Dysregulation of the PI3K/Akt signaling pathway affects cell cycle and apoptosis of side population cells in nasopharyngeal carcinoma.
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DOI：
10.3892/ol.2015.3218
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发表时间：
2015-07
期刊：
影响因子：
2.9
通讯作者：
Danwei Zheng;Guangchao Zhu;Shan Liao;W. Yi;Geng-qiu Luo;Junyu He;Z. Pei;Gui-yuan Li;Yanhong Zhou
中科院分区：
文献类型：
--
作者：
Danwei Zheng;Guangchao Zhu;Shan Liao;W. Yi;Geng-qiu Luo;Junyu He;Z. Pei;Gui-yuan Li;Yanhong Zhou
越来越多的证据表明，某些类型的癌症具有自己的干细胞样细胞，这些细胞的一个子集，称为侧群（SP），可能在肿瘤发生和癌症治疗中起重要作用。然而，SP细胞在鼻咽癌（NPC）中调控的分子机制仍然是未知的。在本研究中，我们假设磷脂酰肌醇-4,5-二磷酸3激酶(PI3K)/Akt信号通路失调可能影响SP和非SP （NSP）表型。从HK-1鼻咽癌细胞系中鉴定出SP细胞，发现SP细胞中肿瘤干细胞标志物的表达高于NSP细胞。新鲜分选的SP细胞G0/G1期细胞比例明显增加，而NSP细胞大部分处于增殖期。细胞分选后培养48 h， SP细胞和NSP细胞的细胞周期分布差异趋于一致。此外，NSP细胞在分选后24 h的凋亡率高于SP细胞，但在分选后48 h的凋亡率无显著差异。为了阐明SP细胞调控细胞周期和凋亡的潜在机制，我们检测了PI3K/Akt信号通路关键分子的表达水平。新鲜分选（0 h）后，SP细胞中PI3K和Akt上调，14-3-3σ蛋白下调。然而，培养48 h后，SP细胞和NSP细胞之间这些分子的表达没有显著差异。这些结果提示PI3K/Akt信号通路的失调可能与鼻咽癌SP细胞的细胞周期和凋亡有关。然而，需要进一步的研究来阐明这些影响的详细机制。
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.