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| Xiaoliu Powder inhibits hepatocellular carcinoma by suppressing the AKT/mTOR-Rac1 pathway |
| Hits 167 Download times 47 Received:January 08, 2026 |
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| DOI
10.11656/j.issn.1673-9043.2026.05.10 |
| Key Words
Xiaoliu Powder;hepatocellular carcinoma;Rac1;AKT/mTOR pathway |
| Author Name | Affiliation | E-mail | | WAN Chengyi | Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China | | | CHENG Yang | Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China | | | WU Mei | Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China | wumei84417@163.com | | GU Qiqun | Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China | | | HUANG Hui | Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China | |
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| Abstract
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| [Objective] Exploring the inhibitory effect and mechanism of the Xiaoliu Powder（XLS），which has the functions of strengthening the spleen，eliminating masses，reinforcing healthy qi，and dispelling pathogenic factors， on the growth of a hepatocellular carcinoma（HCC）bearing nude mouse model and the hepatocellular carcinoma cell line HepG2. [Methods] Animal experiment：HepG2 xenograft mouse model was established，24 nude mice were randomly divided into 4 groups（n=6 per group）：model group（normal saline），XLS low-dose（12.5 g/kg），medium- dose（25 g/kg），and high-dose（50 g/kg）groups. Subcutaneous injection of 8×106 HepG2 cells was performed. After tumor formation，drugs were administered via gastric gavage for 14 days. Tumor size，liver，and spleen indices were recorded. HE staining assessed tumor pathology. Serum levels of alanine aminotransferase（ALT），aspartate aminotransferase（AST），total bilirubin（TBil），gamma-glutamyl transferase（GGT），and alkaline phosphatase（ALP） were measured biochemically. Immunohistochemistry（IHC）detected Ki67 and CD31 expression in tumor tissues. Western blot（WB）analyzed the expression of AKT，p-AKT，mTOR，p-mTOR，PI3K，and Ras-related C3 botulinum toxin substrate 1（Rac1）in tumors. Cell experiment：HepG2 cells were treated with XLS-L（1.25 mg/mL），XLS-M （1.5 mg/mL），and XLS-H（1.75 mg/mL）. The half-maximal inhibitory concentration（IC50）was determined by the CCK-8 assay. The transwell assay assessed cell invasion. Flow cytometry measured apoptosis. Rac1-overexpressing HepG2 cells（HepG2 -Rac1OE）were constructed and divided into XLS（1.5 mg/mL），Rac1OE，Rac1OE + XLS，and control groups. WB detected AKT，p-AKT，mTOR，p-mTOR，and PI3K expression. [Results] Animal experiment： HE staining revealed numerous tumor cells in the model group. Compared to the model group，tumor volume significantly decreased in the XLS medium and high-dose groups（P<0.05），and spleen weight decreased in the XLS high-dose group（P<0.05）. Serum AST，TBil，and GGT levels decreased in all XLS-treated groups（P<0.01）. HE staining of XLS-treated groups showed tumor cell necrosis，cytoplasmic vacuolation，and nuclear pyknosis. Ki67 expression decreased in the XLS high-dose group（P<0.05）. Rac1 expression decreased in the XLS medium-dose group（P<0.01）. Rac1，p-AKT，p-mTOR，and PI3K expression decreased in the XLS high-dose group（P<0.05，P<0.01）.Cell experiment：Cell viability decreased with increasing XLS concentration；the IC50 was approximately 1.5 mg/mL. Cell invasion ability was significantly weakened（P<0.01），and the apoptosis rate increased. The highest apoptosis rate occurred after 72h treatment with 1.5 mg/mL XLS（P<0.01）. Compared to the control group，p-AKT and p-mTOR expression decreased in the XLS group（P<0.05）. Compared to the Rac1OE group，p-AKT and p- mTOR expression decreased in the Rac1OE + XLS group（P<0.05，P<0.01）. [Conclusion] 1）Xiaoliu Powder can inhibit tumor growth in HCC-bearing nude mice，improve liver function，and reduce the expression of proteins in the AKT/mTOR-Rac1 signaling pathway.2）Xiaoliu Powder can inhibit HepG2 cell proliferation，reduce migration and invasion，and promote apoptosis，potentially through suppressing the AKT/mTOR-Rac1 pathway. |
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