Bai Yanxia, Shao Yuan, Li Huajing, Xue Wanli, Quan Fang, Wu Shengli
Department of Otorhinolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Public Health, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
Oncol Lett. 2016 Oct;12(4):2641-2647. doi: 10.3892/ol.2016.4980. Epub 2016 Aug 8.
Ki-67 is one of the most useful markers to evaluate cell proliferative activity and has been widely used in tumor treatment and research. However, its role in human laryngeal carcinoma remains poorly defined. The aim of the present study was to investigate the expression of Ki-67 in human laryngeal squamous carcinoma and the effect of Ki-67 gene silencing by small interfering (si)RNA on the proliferation of human laryngocarcinoma HEp2 cells. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were performed to examine the expression of Ki-67 in human laryngeal squamous carcinoma tissues and adjacent non-cancer tissues from 50 patients with laryngeal squamous carcinoma. RNA interference was used to knock down the expression of Ki-67 in the HEp2 cell line, and the proliferation of the treated cells was observed . Western blot analysis was used to determine the expression levels of epidermal growth factor receptor (EGFR) and E-cadherin in the treated cells. The expression of Ki-67 in the laryngeal squamous carcinoma tissues was significantly higher than that of the adjacent non-tumor tissues (P=0.028). The high expression of Ki-67 in cancer was significantly correlated with cervical lymph node metastasis and clinical outcomes (all P<0.001). The silencing of Ki-67 resulted in the inhibition of proliferation of the HEp2 human laryngocarcinoma cells (P<0.001). In addition, compared with the control group, the expression levels of EGFR and E-cadherin in the Ki-67 siRNA-treated cells were significantly decreased (P<0.001) and increased (P<0.001), respectively. These results suggested that Ki-67 is important in regulating the proliferation of human laryngocarcinoma HEp2 cells and that the mechanism may at least partially be associated with the upregulation of EGFR and the downregulation of E-cadherin. Overall, Ki-67 can be used as an important indicator for judging clinical progress and estimating prognosis in human laryngeal squamous carcinoma.
Ki-67是评估细胞增殖活性最有用的标志物之一,已广泛应用于肿瘤治疗和研究。然而,其在人喉癌中的作用仍不清楚。本研究的目的是探讨Ki-67在人喉鳞状细胞癌中的表达以及小干扰(si)RNA沉默Ki-67基因对人喉癌细胞系HEp2增殖的影响。采用免疫组织化学和逆转录定量聚合酶链反应检测50例喉鳞状细胞癌患者喉鳞状癌组织及癌旁非癌组织中Ki-67的表达。采用RNA干扰技术敲低HEp2细胞系中Ki-67的表达,并观察处理后细胞的增殖情况。采用蛋白质免疫印迹分析检测处理后细胞中表皮生长因子受体(EGFR)和E-钙黏蛋白的表达水平。喉鳞状癌组织中Ki-67的表达明显高于癌旁非肿瘤组织(P=0.028)。癌组织中Ki-67的高表达与颈部淋巴结转移及临床预后显著相关(均P<0.001)。Ki-67基因沉默导致HEp2人喉癌细胞增殖受到抑制(P<0.001)。此外,与对照组相比,Ki-67 siRNA处理组细胞中EGFR的表达水平显著降低(P<0.001),E-钙黏蛋白的表达水平显著升高(P<0.001)。这些结果提示,Ki-67在调控人喉癌细胞系HEp2的增殖中起重要作用,其机制可能至少部分与EGFR的上调和E-钙黏蛋白的下调有关。总体而言,Ki-67可作为判断人喉鳞状细胞癌临床进展和评估预后的重要指标。