Xiaochaihu decoction induces Bel-7402/5-FU cell apoptosis and autophagy via PI3K/AKT/mTOR pathway

Abstract

Objective: This study aimed to observe the inhibitory effects of xiaochaihu decoction (XCHD) on human hepatocellular carcinoma (HCC) cells resistant to 5-fluorouracil (5-FU) (Bel-7402/5-FU) in vitro and in vivo and investigate its possible mechanisms. Methods: Bel-7402 ​cells and their resistant cells to 5-FU (Bel-7402/5-FU) were cultured, and a xenograft was established in nude mice. MTT assays were used to detect the cell viability after XCHD treatment, and an inverted phase contrast microscope was used to observe the morphology and flow cytometry and TUNEL assays were used to determine XCHD-induced apoptosis. Western blot was used to detect Bax and Bcl-2 expressions. Cyto-ID staining was used to assess XCHD-induced autophagy, and the autophagy-related protein (LC3, p62, and beclin) was determined. Finally, the PI3K/AKT/mTOR pathway was detected. Results: Bel-7402/5-FU cells were more resistant to 5-FU compared with Bel-7402 ​cells (P ​< ​0.05), thus XCHD could inhibit the viability of Bel-7402/5-FU cells. Further, XCHD promoted Bel-7402/5-FU cell apoptosis via inducing Bax expression and deducing Bcl-2 expression in vitro and in vivo. Similarly, XCHD promoted autophagy of Bel-7402/5-FU cells by regulating related protein expression. Finally, XCHD blocked the PI3K/AKT/mTOR pathway. Conclusion: XCHD induces Bel-7402/5-FU cell apoptosis and autophagy via blocking the PI3K/AKT/mTOR pathway which is one of the important mechanisms by which XCHD reverses the multidrug resistance of HCC.

Keywords

• Xiaochaihu decoction
• Hepatocellucar carcinoma
• Multidrug resistance
• Apoptosis
• Autophagy
• PI3K/AKT/mTOR pathway