A traditional Chinese medicine decoction developed based on the theory of “Yang transforming into Qi with Yin constituting Form” suppresses hepatic tumorigenesis in mouse models
Background Also the traditional Chinese medicine (TCM) theory of "Yang transforming into Qi with Yin constituting Form" was recognized as a potential mechanism underlying the tumorigenesis. The decoction based on this theory and the underlying molecular mechanisms remained exploration. Methods A TCM decoction was prepared based on "Yang transforming into Qi with Yin constituting Form". Its anti-tumorigenesis effect was evaluated on mouse models of hepatocellular carcinoma (HCC) (H-rasG12V transgenic mice (Ras-Tg) and Diethylnitrosamine (DEN)-induced HCC mice) by liver/body weight, number and size of tumors, histopathological changes and serum biochemistry. RNA sequencing was utilized to check differentially expressed genes (DEGs) and gene ontology (GO) and KEGG were used for bioinformatics analysis. The concerned biological processes were further confirmed by RT-qPCR and metabolite detection kits. Results The TCM decoction significantly suppressed both Ras oncogene- and DEN-induced hepatic tumorigenesis evidenced by reduced serum ALT and AST levels, liver weight, liver/body weight ratio, hepatic tumor numbers and sizes. RNA sequencing showed 659 up-regulated genes and 222 down-regulated genes in comparison of liver tissues between TCM-treated and untreated Rag-Tg (n=5). GO entries and KEGG analysis revealed multiple biological processes and pathways involving the hepatic tumorigenesis suppressing effective of the TCM. Further molecular examination confirmed that activation of retinal metabolism, reduction of ROS and electrophilic levels by inhibiting the H2O2 production and promoting GSH production, and inhibition of expression of inflammation factors play pivotal roles in the anti-tumorigenesis effects of TCM. Conclusion A TCM decoction based on "Yang transforming into Qi with Yin constituting Form" showed effective anti-hepatic tumorigenesis functions and its regulation functions on retinal, ROS and inflammation processes play important roles. The present study provides valuable clue for clinical therapy on tumorigenesis. Overall design: Firstly, develop and prepare traditional Chinese medicine decoctions, and confirm the anti liver tumor occurrence or development effect of TCM by feeding Ras oncogene and DEN induced HCC mouse models. Perform bioinformatics analysis to investigate potential mechanisms by sequencing RNA from peri-tumor and tumor tissues.