Effect of Biejia Decoction Pill on aerobic glycolysis in hepatocellular carcinoma by regulating the protein kinase B/mammalian target of rapamycin signaling pathway

Qinwen TAN, Jingjing HUANG, Ruixi ZHONG, Yuanqin DU, Jian XU, Jinli NONG, Yujiao PENG

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Journal of Clinical Hepatol ›› 2025, Vol. 41 ›› Issue (2) : 300-306. DOI: 10.12449/JCH250216
Liver Neoplasm

Effect of Biejia Decoction Pill on aerobic glycolysis in hepatocellular carcinoma by regulating the protein kinase B/mammalian target of rapamycin signaling pathway

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Abstract

Objective To investigate the inhibitory effect of Biejia Decoction Pill on the proliferation， migration， and aerobic glycolysis of hepatocellular carcinoma （HCC） using cell experiments， as well as related mechanisms. Methods Human liver cancer cell line Huh7 was selected， and Sprague-Dawley rats were randomly divided into blank serum group， inhibitor group， and high-， middle-， and low-dose Biejia Decoction Pill groups. Rat serum containing the drug was prepared for the incubation of Huh7 cells. CCK8 assay and scratch assay were used to explore the effect of Biejia Decoction Pill on the proliferation and migration of HCC cells； glycolytic rate-limiting enzymes and metabolites were measured to explore the effect of Biejia Decoction Pill on aerobic glycolysis of liver cancer cells； RT-qPCR and Western blot were used to explore the effect of Biejia Decoction Pill on the mRNA expression， related proteins， and phosphorylation of the protein kinase B （AKT）/mammalian target of rapamycin （mTOR） signaling pathway. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Dunnett’s T3 test were used for further comparison between two groups. Results Compared with the blank serum group， the Biejia Decoction Pill groups had significant reductions in OD value， migration rate during different periods of time， glycolytic rate-limiting enzymes （hexokinase， phosphofructokinase， pyruvate kinase）， and glycolytic metabolites （pyruvate， lactic acid， ATP） （all P<0.05）. RT-qPCR results showed that compared with the blank serum group， the high-， middle-， and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of mTOR， and the high- and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of AKT （all P<0.05）. Western blot results showed that compared with the blank serum group， the high-， middle-， and low-dose Biejia Decoction Pill groups had significant reductions in the expression levels of mTOR-related proteins and phosphorylated proteins， and the high- and middle-dose Biejia Decoction Pill groups had significant reductions in the expression levels of AKT-related proteins and phosphorylated proteins （all P<0.05）. Conclusion This study preliminarily verifies that the serum containing Bijia Decoction Pill can inhibit the aerobic glycolysis of human hepatoma Huh7 cells， thereby inhibiting their proliferation and migration， possibly by inhibiting the expression of the proteins related to the AKT/mTOR signaling pathway.

Key words

Bie Jia Jian Wan / Liver Neoplasms， Experimental / Warburg Effect， Oncologic

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Qinwen TAN , Jingjing HUANG , Ruixi ZHONG , et al . Effect of Biejia Decoction Pill on aerobic glycolysis in hepatocellular carcinoma by regulating the protein kinase B/mammalian target of rapamycin signaling pathway. Journal of Clinical Hepatol. 2025, 41(2): 300-306 https://doi.org/10.12449/JCH250216

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Funding

Guangxi Natural Science Foundation(2022GXNSFAA035460)
Guangxi Graduate Education Innovation Program(YCSW2023395)
Guangxi University of Traditional Chinese Medicine Introduction of Doctoral Research Fund Project(2022BS026)

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