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Xihuang Wan mediates glycolysis and inhibits lung cancer development by downregulating the AKT/STAT3 pathway
Xiaoliang Han1, Tong Liu2, Jinrong Huang3
1Department of Thoracic Surgery, Affiliated Hospital of Shaoxing University (The Shaoxing Municipal Hospital), Shaoxing 312000, China.
Abstract:
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.
Insights
Xihuang Wan (XHW) significantly inhibits lung cancer cell growth and glycolysis by downregulating the AKT-STAT3 pathway. This traditional Chinese medicine shows promise in treating lung cancer by targeting key metabolic processes.
Area of Science:
- Oncology
- Metabolic pathways
- Traditional Chinese Medicine
Background:
- Glycolysis is crucial for lung cancer cell proliferation and survival.
- Targeting cancer metabolism offers a potential therapeutic strategy.
Purpose of the Study:
- To investigate the effect of Xihuang Wan (XHW) on lung cancer glycolysis.
- To elucidate the underlying molecular mechanisms involving the AKT-STAT3 pathway.
Main Methods:
- In vitro studies using A549 lung cancer cells treated with XHW, AKT activator SC79, and AKT inhibitor MK-2206.
- In vivo studies using a lung cancer mouse model treated with XHW.
- Assays included cell proliferation, migration, invasion, apoptosis, cell cycle analysis, glucose uptake, extracellular acidification rate, and Western blotting for protein expression.
Main Results:
- XHW inhibited A549 cell proliferation, migration, invasion, and induced apoptosis and G1 cell cycle arrest.
- XHW markedly reduced glycolysis, evidenced by decreased glucose uptake, metabolic products, extracellular acidification rate, and glycolysis-related proteins.
- XHW downregulated the AKT-STAT3 pathway, with effects partially reversed by SC79 and enhanced by MK-2206.
- In vivo, XHW inhibited tumor growth and improved lung pathology in mice, reducing glycolysis and AKT-STAT3 pathway proteins.
Conclusions:
- Xihuang Wan (XHW) demonstrates significant anti-lung cancer effects by inhibiting glycolysis.
- The mechanism involves the downregulation of the AKT-STAT3 signaling pathway.
- XHW represents a potential therapeutic agent for lung cancer treatment targeting metabolic reprogramming.
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