Zhang Gong, Zhang Shuping, Ren Jinjin, Yao Chunxiao, Zhao Zhongren, Qi Xiurong, Zhang Xiaofeng, Wang Shuye, Li Lei
Department of Radiotherapy, People's Hospital of Shanxi Province, Taiyuan, Shanxi 030012, P.R. China.
Oncol Lett. 2018 Aug;16(2):2495-2500. doi: 10.3892/ol.2018.8923. Epub 2018 Jun 7.
Tumor recurrence and metastasis of nasopharyngeal cancer (NPC) often result in the failure of treatment due to chemoradioresistance. Cancer stem cells (CSCs) have been observed to drive tumor initiation and tumor chemoradioresistance. Therefore, the poor prognosis of advanced NPC is likely to result from the failure to kill CSCs. Sphere formation may be used as an experimental method to enrich potential CSC subpopulations. At present, there are few reports on NPC tumorspheres. The present study focused on examining the cancer stem-like properties of NPC tumorspheres from NPC cell lines. Western blot analysis revealed that NPC tumorspheres had a higher expression of stem cell markers Nanog homeobox and SRY-box 2, compared with parental cells. It was additionally verified that NPC tumorspheres contained a high aldehyde dehydrogenase (ALDH) enzymatic activity compared with parental cells. ALDH+ cells were amplified by 9- to 10-fold in tumorspheres, compared with parental cells (1.8 vs. 16.9%). The tumorsphere cells exhibited an increased half maximal inhibitory concentration value of >10-fold with cisplatin compared with the control parental cells. Compared with the parental cells, the percentage of side population cells in the tumorsphere cell population increased significantly (10.3 vs. 2.3%; P<0.05). NPC tumorsphere cells demonstrated enhanced resistance to radiation. Further investigation verified that salinomycin inhibited NPC CSCs by selectively targeting its stem cells. Altogether, the data revealed that NPC tumorspheres contain cancer stem-like populations with increased chemoradioresistance. It was suggested that the serum-free culture of NPC cells may provide an appropriate model for researching the sensitivity of CSCs to therapeutic agents. It was additionally revealed that salinomycin is an efficient inhibitor of NPC CSCs, supporting the hypothesis that salinomycin may eliminate CSCs and imply a need for further clinical evaluation.
鼻咽癌（NPC）的肿瘤复发和转移常因放化疗耐药而导致治疗失败。已观察到癌症干细胞（CSCs）驱动肿瘤起始和肿瘤放化疗耐药。因此，晚期鼻咽癌预后较差可能是由于未能杀死癌症干细胞。成球实验可作为富集潜在癌症干细胞亚群的实验方法。目前，关于鼻咽癌肿瘤球的报道较少。本研究聚焦于检测来自鼻咽癌细胞系的鼻咽癌肿瘤球的癌症干细胞样特性。蛋白质印迹分析显示，与亲代细胞相比，鼻咽癌肿瘤球中干细胞标志物同源盒蛋白Nanog和SRY盒转录因子2的表达更高。此外还证实，与亲代细胞相比，鼻咽癌肿瘤球具有较高的醛脱氢酶（ALDH）酶活性。与亲代细胞相比（1.8%对16.9%），肿瘤球中ALDH+细胞扩增了9至10倍。与对照亲代细胞相比，肿瘤球细胞对顺铂的半数最大抑制浓度值增加了10倍以上。与亲代细胞相比，肿瘤球细胞群体中旁群细胞的百分比显著增加（10.3%对2.3%；P<0.05）。鼻咽癌肿瘤球细胞对辐射的抗性增强。进一步研究证实，沙林霉素通过选择性靶向其干细胞来抑制鼻咽癌癌症干细胞。总之，数据显示鼻咽癌肿瘤球含有具有增强放化疗耐药性的癌症干细胞样群体。提示鼻咽癌细胞的无血清培养可为研究癌症干细胞对治疗药物的敏感性提供合适模型。此外还发现沙林霉素是鼻咽癌癌症干细胞的有效抑制剂，支持沙林霉素可能消除癌症干细胞的假说，并意味着需要进一步的临床评估。
