The anti-tumor effect of Xuanfuhua decoction combined with sorafenib on liver cancer bearing mice based on PTEN/PI3K/AKT signaling pathway
- VernacularTitle:基于PTEN/PI3K/AKT信号通路探讨旋覆花汤联合索拉非尼对肝癌荷瘤小鼠的抗肿瘤作用
- Author:
Qian-Qian SU
1
;
Liang HAN
;
Wen-Zhao LUO
;
Chang-Pu ZHAO
Author Information
- Keywords: Xuanfuhua decoction; sorafenib; liver cancer; apoptosis; phosphatase and tensin homolog/phosphatidylinositol-3-kinase/protein kinase B path-way; proliferation
- From: Chinese Pharmacological Bulletin 2024;40(10):1884-1892
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of Xuanfuhua decoction combined with sorafenib on liver cancer bearing mice and the underlying mechanism.Methods KM mice were divided into the liver cancer group,Xuanfuhua decoction group,sorafenib group,combina-tion group,combination+PTEN inhibitor(BPV)group,combination+PI3K activator(IGF-1)group and blank group.Liquid chromatography-mass spec-trometry was used to detect the blood components of Xuanfuhua decoction in serum of mice in liver cancer group and Xuanfuhua decoction group.The changes of serum ALT,AST,tumor weight and tumor volume were detected.The pathological changes of tumor tissue,the proportion of TUNEL,p53 and Bax positive cells,the levels of IFN-γ and TNF-α,and the protein changes of PTEN,p-PI3K and p-AKT were detected.The effects of combined treatment on the proliferation and apopto-sis of H22 cells of mouse hepatoma were observed in vitro.Results There were 11 constituents absorbed into blood of Xuanfuhua decoction.Compared with the liver cancer group,the tumor cells in the Xuanfuhua decoction group,sorafenib group,and combination group were dispersed,the serum AST and ALT levels,tumor weight,tumor volume,and p-PI3K and p-AKT proteins decreased,the proportion of TUNEL,p53 and Bax positive cells,IFN-γ,TNF-α levels,and PTEN protein in tumor tissue increased,and the trend of the combination group was the most obvious(P＜0.05).BPV or IGF-1 reversed the anti-tumor effect of the combined treatment on liver cancer bearing mice.In vitro experiments showed that the combined treatment could inhibit the proliferation of H22 cells and promote the apoptosis of H22 cells better than Xuanfuhua de-coction or sorafenib alone.BPV or IGF-1 reversed the effects of combined treatment on the proliferation and apoptosis of H22 cells.Conclusion Xuanfuhua de-coction combined with sorafenib may exert anti-tumor effect on liver cancer bearing mice by up-regulating PTEN and inhibiting PI3K/AKT pathway.
