The effect and mechanism of hexokinase-2 on cisplatin resistance in lung cancer cells A549

Background: Hexokinase (HK) is the first rate-limiting Enzyme of glycolysis, which can convert glucose to glucose-6-phosphate. There are several subtypes of HK, including HK2, which is highly expressed in a variety of different tumors and is closely associated with survival.

Methods: Non-small cell lung Cancer (NSCLC) A549 cells with stable overexpression and knockdown of HK2 were obtained by lentivirus transfection. The effects of overexpression and knockdown of HK2 on proliferation, migration, invasion, and glycolytic activity of A549 cells were investigated. The effects on Apoptosis were also analyzed using western blot and flow cytometry. In addition, the mitochondria and cytoplasm were separated and the expression of apoptotic proteins was detected by western blot respectively.

Results: Upregulation of HK2 could promote glycolysis, cell proliferation, migration, and invasion, which would be inhibited through the knockdown of HK2. HK2 overexpression contributed to cisplatin resistance, whereas HK2 knockdown enhanced cisplatin-induced Apoptosis in A549 cells.

Conclusions: Overexpression of HK2 can promote the proliferation, migration, invasion, and drug resistance of A549 cells by enhancing aerobic glycolysis and inhibiting Apoptosis. Reducing HK2 expression or inhibiting HK2 activity can inhibit glycolysis and induce Apoptosis in A549 cells, which is expected to be a potential treatment method for NSCLC.

HK2; ROS; aerobic glycolysis; drug resistance; mitochondrial apoptosis.