Xihuang Wan mediates glycolysis and inhibits lung cancer development by downregulating the AKT/STAT3 pathway.

Glycolysis activation is a prominent feature of lung cancer, and this metabolic transformation is essential for the growth of cancer cells. The research intended to investigate the role of Xihuang Wan (XHW) in lung cancer-associated glycolysis. Lung cancer cell line A549 was treated with 20 % XHW drug-containing serum (XHW-DS). To further investigate the underlying mechanism, cells were treated with the AKT activator SC79 and AKT inhibitor MK-2206. XHW significantly induced apoptosis and G1 phase cell cycle arrest, and inhibited the proliferation, migration, and invasion of A549 cells. XHW markedly inhibited glycolysis, as evidenced by decreased glucose uptake and its metabolic products, along with reduced extracellular acidification rate and glycolysis-related protein levels. Moreover, XHW notably downregulated AKT-STAT3 pathway. Importantly, the effects of XHW on A549 cells were partially reversed by SC79 and enhanced by MK-2206. Nude mice were injected subcutaneously with A549 cells to establish a lung cancer mouse model, and then administered XHW or DDP (a positive control drug). In lung cancer mice, XHW significantly inhibited tumor growth and improved lung pathological changes. Additionally, XHW obviously reduced glycolysis-related and AKT-STAT3 pathway protein expression. In conclusion, these findings revealed that XHW inhibits glycolysis in lung cancer by downregulating AKT-STAT3 pathway.