Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide, with a five-year survival rate of only 18%. Non-small cell lung cancer (NSCLC) in addition to large cell lung cancer, comprise 85%-90% of all lung cancer diagnoses. Chemoresistance of the cancer cells is one of the reasons for the poor survival rate. In this research, we used mitoxantrone-induced resistant (MXR) NCl-H460 cells to find the mechanism of chemoresistance. We found that the MXR-resistant cells had high single-cell clonogenic ability like cancer stem cells. From the quantitative proteomics study, we found that the MXR-resistant cells high upregulated many metabolism and stem cell-related proteins, such as STAT3 and ALDH. The high level expression of histone 3.1 showed the possibility of genetic changing of resistant cells. Using Western blot assays, we confirmed enhancement of EZH2 in MXR-resistant NCl-H460 cells. Therefore, the EZH2-STAT3 pathway has an important role in the MXR-resistant NCI-H460 cancer cells. Both EZH2 and STAT3 can be used as new target proteins for chemotherapy in the treatment of large cell lung cancer.