Unveiling the Mechanism of Compound Ku-Shen Injection in Liver Cancer Treatment through an Ingredient-Target Network...

Area of Science:

• Integrative oncology
• Traditional Chinese Medicine (TCM) pharmacology
• Network pharmacology

Background:

• Compound Ku-Shen Injection (CKI) is a TCM preparation used for advanced cancers, including liver cancer.
• The precise mechanisms of CKI's anti-cancer effects remain largely undefined.
• Investigating CKI's action is crucial for understanding its therapeutic potential in oncology.

Purpose of the Study:

• To elucidate the therapeutic mechanisms of CKI in liver cancer treatment.
• To explore the TCM compatibility theory underlying CKI's efficacy.
• To validate findings through molecular docking and in vitro experiments.

Main Methods:

• Network pharmacology identified 16 active components and 193 potential targets for CKI in liver cancer.
• Key targets such as EGFR and ESR1 were pinpointed.
• KEGG pathway analysis highlighted neuroactive ligand-receptor interaction, cAMP signaling, and serotonergic synapses.
• Molecular docking and in vitro assays (CCK-8, Western blot) validated component-target interactions and anti-cancer effects.

Main Results:

• CKI targets key proteins including EGFR and ESR1 in liver cancer.
• The neuroactive ligand-receptor interaction and cAMP signaling pathways are implicated in CKI's action.
• Oxymatrine and matrine, key CKI components, inhibit HepG2 liver cancer cell proliferation.
• Oxymatrine was shown to suppress EGFR expression, contributing to therapeutic efficacy.

Conclusions:

• This study elucidates the therapeutic mechanism of CKI in liver cancer.
• The underlying principles of CKI's TCM compatibility were revealed through its mode of action.
• Findings provide a scientific basis for CKI's use in liver cancer treatment.