Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma
Qing-Ping Deng1, Mao-Jie Wang1, Xing Zeng1
1The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
Background:
Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2) in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer.
Methods:
Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα). The animal model was confirmed by the hematoxylin and eosin (H&E) method. Tumor-bearing mice were then administered graded concentrations of glycyrrhizin, cisplatin or both. After the treatments, body weights of all animals were recorded, and immunohistochemistry staining of lung tissues and serum biochemistry detection of aspartate amino transferase (AST), alanine amino transferase (ALT), urea and creatinine were carried out.
Results:
Treatment with glycyrrhizin alone or the combination of cisplatin and glycyrrhizin profoundly reduced expression of thromboxane synthase (TxAS) as well as proliferating cell nuclear antigen (PCNA), recovered the body weight, and rescued damage of liver and kidney in tumor-bearing mice. Although it inhibited PCNA expression, cisplatin could not significantly suppress TxAS expression. Because of a positive feedback loop between TPα and TxAS, the effects of glycyrrhizin are possibly attributable to the suppression of the TxA2 pathway.
Conclusions:
This study provides in vivo evidence to support glycyrrhizin as a potential candidate for developing new regimens to overcome tumor progression and the resistance and toxicity of cisplatin.
Insights
Glycyrrhizin shows potential as an anti-cancer agent, effectively reducing tumor progression and mitigating cisplatin toxicity in animal models by suppressing the thromboxane A2 (TxA2) pathway.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Global search for low-toxicity anti-cancer agents is ongoing.
- Glycyrrhizin demonstrates anti-cancer properties and low toxicity by suppressing thromboxane A2 (TxA2) in lung cancer cell lines.
- In vivo validation of glycyrrhizin's anti-cancer effects in lung cancer animal models is needed.
Purpose of the Study:
- To evaluate the efficacy of glycyrrhizin in an in vivo model of lung adenocarcinoma.
- To investigate the effects of glycyrrhizin, alone and in combination with cisplatin, on tumor progression and toxicity.
- To elucidate the mechanism of action of glycyrrhizin in suppressing the thromboxane A2 (TxA2) pathway.
Main Methods:
- Human lung adenocarcinoma xenografts were established in nude mice.
- Mice were treated with glycyrrhizin, cisplatin, or a combination.
- Tumor growth, body weight, liver and kidney function, and expression of key proteins (TxAS, PCNA) were assessed.
Main Results:
- Glycyrrhizin, alone or with cisplatin, reduced tumor progression markers (TxAS, PCNA) and improved host parameters (body weight, organ function).
- Cisplatin inhibited PCNA but not TxAS, suggesting a different primary mechanism.
- Glycyrrhizin's effects are linked to suppression of the TxA2 pathway, potentially via a feedback loop involving TPα and TxAS.
Conclusions:
- Glycyrrhizin demonstrates in vivo anti-cancer activity against lung adenocarcinoma.
- Glycyrrhizin can potentially overcome tumor progression and cisplatin resistance.
- Glycyrrhizin may reduce the toxicity associated with cisplatin treatment, offering a promising therapeutic strategy.
