Xiao Mingbing, Li Tao, Ji Yifei, Jiang Feng, Ni Wenkai, Zhu Jing, Bao Baijun, Lu Cuihua, Ni Runzhou
Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Department of Medical Oncology, Nantong Tumor Hospital, Nantong, Jiangsu 226361, P.R. China.
Oncol Lett. 2018 Jan;15(1):175-182. doi: 10.3892/ol.2017.7295. Epub 2017 Oct 31.
S100A11, a member of S100 calcium-binding protein family, is associated with the numerous processes of tumorigenesis and metastasis. In the present study, the role of S100A11, and its possible underlying mechanisms in cell proliferation, apoptosis and cell cycle distribution in human pancreatic cancer were explored. Immunohistochemical analyses of S100A11 and phosphorylated (p)-AKT serine/threonine kinase (AKT) were performed in 30 resected specimens from patients with pancreatic cancer. PANC-1 cells were transfected with pcDNA3.1-S100A11 or treated with 50 µmol/l LY294002 for 48 h. Cell proliferation was determined using a cell counting kit-8 assay, whereas apoptosis and cell cycle distribution were determined by flow cytometry analysis. The mRNA and protein levels of S100A11, and AKT were determined using semi quantitative reverse transcription-polymerase chain reaction and western blot analyses, respectively. Pearson correlation analysis revealed that the expression levels of S100A11 and p-AKT were positively correlated (r, 0.802; P<0.05). Compared with the control group, S100A11 overexpression significantly promoted PANC-1 cell proliferation and reduced the percentage of early apoptotic cells. Flow cytometric analysis indicated that the proportion of PANC-1 cells in the S phase was significantly elevated and cell percentage in the G0/G1 phase declined in response to S100A11 overexpression (all P<0.05). S100A11 overexpression also significantly increased AKT mRNA and p-AKT protein expression levels (both P<0.05). The phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, significantly inhibited PANC-1 cell proliferation, promoted apoptosis and caused G1/S phase arrest in PANC-1 cells (all P<0.05). These findings together suggest that S100A11 promotes the viability and proliferation of human pancreatic cancer PANC-1 cells through the upregulation of the PI3K/AKT signaling pathway. Thus, S100A11 may be considered as a novel drug target for targeted therapy of pancreatic cancer.
S100A11是S100钙结合蛋白家族的成员之一,与肿瘤发生和转移的众多过程相关。在本研究中,探讨了S100A11在人胰腺癌细胞增殖、凋亡及细胞周期分布中的作用及其潜在机制。对30例胰腺癌患者的手术切除标本进行了S100A11和磷酸化(p)-AKT丝氨酸/苏氨酸激酶(AKT)的免疫组织化学分析。用pcDNA3.1-S100A11转染PANC-1细胞或用50μmol/L LY294002处理48小时。使用细胞计数试剂盒-8检测法测定细胞增殖,而通过流式细胞术分析测定凋亡和细胞周期分布。分别使用半定量逆转录-聚合酶链反应和蛋白质印迹分析来测定S100A11、AKT的mRNA和蛋白质水平。Pearson相关性分析显示,S100A11和p-AKT的表达水平呈正相关(r = 0.802;P<0.05)。与对照组相比,S100A11过表达显著促进PANC-1细胞增殖并降低早期凋亡细胞的百分比。流式细胞术分析表明,响应S100A11过表达,PANC-1细胞在S期的比例显著升高,而在G0/G1期的细胞百分比下降(所有P<0.05)。S100A11过表达还显著增加AKT mRNA和p-AKT蛋白表达水平(均P<0.05)。磷酸肌醇3激酶(PI3K)抑制剂LY294002显著抑制PANC-1细胞增殖,促进凋亡并导致PANC-1细胞发生G1/S期阻滞(所有P<0.05)。这些结果共同表明,S100A11通过上调PI3K/AKT信号通路促进人胰腺癌PANC-1细胞的活力和增殖。因此,S100A11可被视为胰腺癌靶向治疗的新型药物靶点。