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肿瘤干细胞的多耐药性是导致肿瘤化疗失败的重要因素之一。因此,鉴定和明确耐药性肺癌干细胞亚群(cancer stem-cell subpopulations)的特征和机制是当前的热点。该研究从肺癌病人的肿瘤组织中分离出一个高表达CD133和ABCG2蛋白的细胞亚群。发现该CD133+/ABCG2+肺癌细胞高表达干细胞的生物标志,如:Nanog、Oct4、Sox2、Nestin、CD44、CD117、CD133和ABCG2等。不仅如此,这群细胞在体外具有高增殖性和高侵袭性,对于多种常用的化疗药物(如:顺铂和吉西他滨等)都具有耐受性。而且,少量的CD133+/ABCG2+肺癌细胞即可以在免疫缺陷小鼠体内形成肿瘤。为了研究耐药性机制,我们检测了CD133+/ABCG2+中ABCG2基因启动子区域的CpG岛(CpG islands)DNA甲基化修饰状态。实验结果表明,该细胞中,ABCG2基因启动子区域的CpG岛处于去甲基化修饰状态。综上所述,作者成功地从肺癌病人肿瘤组织中分离、富集得到了CD133+/ABCG2+细胞亚群,并利用该群细胞在体外建立了肿瘤耐药性研究模型。对于肺癌CD133+/ABCG2+细胞的研究可为开发肺癌个体化治疗和新型化疗药物的设计和研发提供理论依据。
Multidrug resistance of cancer stem cells is one of the important factors leading to the failure of chemotherapy. Therefore, the features and mechanisms of identifying and definitively drug-resistant cancer stem-cell subpopulations are the current hot spots. The study isolated a subset of cells that highly expressed CD133 and ABCG2 proteins from lung cancer patients. The biomarkers of high expression of stem cells such as Nanog, Oct4, Sox2, Nestin, CD44, CD117, CD133 and ABCG2 were found in the CD133 + / ABCG2 + lung cancer cells. Moreover, these cells are highly proliferative and aggressive in vitro and are resistant to a variety of commonly used chemotherapeutic agents, such as cisplatin and gemcitabine. Moreover, small numbers of CD133 + / ABCG2 + lung cancer cells can form tumors in immunodeficient mice. To investigate the drug resistance mechanism, we examined the DNA methylation status of CpG islands in the ABCG2 promoter region in CD133 + / ABCG2 +. The experimental results show that in this cell, the CpG island in the ABCG2 promoter region is in a demethylated state. In conclusion, the authors successfully isolated and enriched CD133 + / ABCG2 + cell subpopulations from lung cancer patients and established a model of tumor drug resistance in vitro. The research of lung cancer CD133 + / ABCG2 + cells can provide the theoretical basis for the development of individualized treatment of lung cancer and the design and development of new chemotherapy drugs.