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Archive > Volume 32 Issue 3 > 2025,32(3):294-300. DOI:10.3872/j.issn.1007-385X.2025.03.009 Prev Next
Basic Research
Asiaticoside inhibits the malignant biological behavior of hepatocellular carcinoma Huh7 cells via the cAMP/PKA/CREB signaling pathway
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Abstract:
[Abstract] Objective: To investigate whether asiaticoside (ASI) regulates the malignant biological behavior of hepatocellular carcinoma Huh7 cells via the cyclic adenosine monophosphate/protein kinase A/cAMP-response element binding protein (cAMP/PKA/ CREB) signaling pathway. Methods: After determining the suitable ASI concentration and treatment duration using MTT assay, Huh7 cells were divided into the following groups: control, ASI-L (20 μmol/L), ASI-M (40 μmol/L), ASI-H (80 μmol/L), and ASI-H+ Forskolin (80 μmol/L ASI + 100 μmol/L cAMP activator Forskolin) groups. After 48 h of treatment, cell proliferation was assessed using MTT and colony formation assays; cell migration and invasion were analyzed using Transwell assays; apoptosis was detected using an Annexin V-FITC apoptosis detection kit. The secretion level of cAMP and the protein expression levels of phosphorylated PKA (p-PKA) and phosphorylated CREB (p-CREB) were evaluated using ELISA and Western blotting, respectively. A subcutaneous xenograft model was established by injecting Huh7 cells into the right abdomen of nude mice. ASI was administered by gavage at doses of 5, 15, and 45 mg/kg for 4 weeks. Tumors were then harvested and weighed. Results: Treatment with 40 μmol/L ASI for 48 hours (close to the IC??) was determined to be the appropriate concentration and duration. Compared with the control group, the ASI-L, ASI M, and ASI-H groups showed significantly reduced Huh 7 cell proliferation, colony formation, migration, invasion, cAMP levels, and expression of p-PKA/PKA and p-CREB/CREB (all P < 0.05), while apoptosis rates were significantly increased (P < 0.05). Compared with the ASI-H group, the ASI-H + Forskolin group exhibited significantly increased proliferation, colony formation, migration,invasion, cAMP level, and expression of p-PKA/PKA and p-CREB/CREB (all P < 0.05), but apoptosis was significantly reduced (all P < 0.05). In the nude mouse xenograft model, ASI at 5, 15, and 45 mg/kg markedly decreased tumor weight in nude mice (all P < 0.05). Conclusion: ASI inhibits the malignant biological behaviors and promotes apoptosis of Huh7 cells, as well as suppresses tumor growth in nude mice, by downregulating the expression of proteins in the cAMP/PKA/CREB signaling pathway.
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