Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma.
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.
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
Qing-Ping
QP
Deng
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
Mao-Jie
MJ
Wang
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
Xing
X
Zeng
Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong.
George Gong
GG
Chen
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.|University Medical Center Utrecht, Utrecht, the Netherlands.|Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China.
Run-Yue
RY
Huang
D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D019695:Glycyrrhizic Acid; D002945:Cisplatin
Animal model; Cisplatin; Glycyrrhizin; Lung adenocarcinoma; Thromboxane A2