Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan 250012, PR China.
Oncol Rep. 2012 Jul;28(1):147-54. doi: 10.3892/or.2012.1787. Epub 2012 Apr 26.
Lung adenocarcinoma, with increased incidence in the world, exhibits poor prognosis and is usually resistant to conventional chemotherapy due to drug resistance. The enhancer of zeste homologue 2 (EZH2), a histone methyltransferase, plays a key role in tumorigenesis and cancer development through chromatin remodeling in various types of cancer. However, its potential role in lung adenocarcinoma has not been well defined. In this study, the expression of EZH2 was examined in lung adenocarcinoma tissues and cell lines. Most interestingly, EZH2 overexpression was detected in tumor tissue and significantly correlated with histological differentiation, pathological tumor-node-metastasis stage and smoking history, but not with gender or age. Furthermore, EZH2 overexpression was also detected in cisplatin-resistant cancer cells rather than cisplatin-sensitive cells. Short hairpin RNA targeted against EZH2 inhibited cell proliferation and migration, and led to G(2)/M cell cycle arrest and apoptosis in both cisplatin-resistant and cisplatin-sensitive cell lines. Moreover, EZH2 knockdown enhanced cisplatin sensitivity of cisplatin-resistant cells and reduced the expression levels of multidrug resistance-related protein 1. Our study suggests that EZH2 contributes to the progression of lung adenocarcinoma, and the deletion of EZH2 inhibits cancer and resensitizes cells to cisplatin in lung adenocarcinoma.
肺腺癌在全球的发病率不断增加,预后较差,通常对传统化疗具有耐药性。增强子的锌指蛋白 2(EZH2)是一种组蛋白甲基转移酶,通过各种类型癌症中的染色质重塑,在肿瘤发生和癌症发展中发挥关键作用。然而,其在肺腺癌中的潜在作用尚未得到充分定义。在本研究中,检测了肺腺癌组织和细胞系中 EZH2 的表达。最有趣的是,在肿瘤组织中检测到 EZH2 过表达,并且与组织学分化、病理肿瘤-淋巴结-转移分期和吸烟史显著相关,但与性别或年龄无关。此外,还在顺铂耐药癌细胞中检测到 EZH2 过表达,而不是在顺铂敏感细胞中。针对 EZH2 的短发夹 RNA 抑制了细胞增殖和迁移,并导致顺铂耐药和敏感细胞系中的 G2/M 细胞周期停滞和细胞凋亡。此外,EZH2 敲低增强了顺铂耐药细胞对顺铂的敏感性,并降低了多药耐药相关蛋白 1 的表达水平。我们的研究表明,EZH2 促进肺腺癌的进展,EZH2 的缺失抑制肺腺癌细胞的生长并使细胞对顺铂重新敏感。