Abstract: Objective To investigate the changes and effects of glycolysis in Gefitinib resistance in non⁃small cell lung cancer (NSCLC) . Methods NSCLC parental cells PC⁃9 and A549 were cultured in vitro, and NSCLC Gefitinib⁃resistant cells PC⁃9⁃GR and A549⁃GR were constructed by the increasing concentration method. Cell resistance was identified by CCK⁃8 and colony formation assay. The glucose metabolism and lactate production levels were detected using glucose and lactate assay kits, respectively. qRT⁃PCR and Western blot were used to detect the mRNA and protein levels of the key enzymes in glycolysis. After inhibition of glycolysis by 2⁃deoxy⁃D⁃glucose, the viability of cells and the changes of drug resistance to Gefitinib were observed. Results Compared with parental cells, the resistance of PC⁃9⁃GR and A549⁃GR cells to Gefitinib was enhanced (all P<0.01), and glucose metabolism rate and lactate production level were increased (all P<0.01). The mRNA expression levels of HK2, LDHA and PFK and the protein levels of HK2 , LDHA, PFKP and PKM2 were increased (all P<0.001). The inhibitory effect of 2⁃DG on the activities of drug⁃resistant cells was more significant than on those of their respective parental cells (all P<0.05), and to some extent, it could enhance the killing effect of Gefitinib on drug⁃resistant cells. Conclusions Gefitinib resistance in NSCLC is accompanied by the activation of glycolysis, and is associated with increased expression of key enzymes in glycolysis. Inhibiting the levels or activities of glycolysis may be an effective measure to reverse the drug resistance of Gefitinib.

Key words: Non-small cell lung cancer')">Non-small cell lung cancer, Gefitinib, drug?resistance, Glycolysis, Metabolic reprogramming