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.

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