# Elucidating the PTK2-Targeted Anti-Hepatocellular Carcinoma Effects of Euphorbia helioscopia L. via Integrated Network Pharmacology, Mendelian Randomization, and Experimental Validation

## TL;DR

This study explores how the traditional Chinese herb Euphorbia helioscopia fights liver cancer by identifying key compounds and biological pathways involved.

## Contribution

The study identifies PTK2 as a key target of Euphorbia helioscopia in treating hepatocellular carcinoma using integrated pharmacological and experimental methods.

## Key findings

- 104 compounds were identified from Euphorbia helioscopia, with 18 targeting HCC-related proteins.
- PTK2 was confirmed as a core target associated with HCC risk through bioinformatics and Mendelian randomization.
- ZQ inhibited PTK2/PI3K/AKT phosphorylation and suppressed tumor growth in mice.

## Abstract

Euphorbia helioscopia L. (Zeqi, ZQ) is a traditional Chinese herb used to treat various tumors, but its molecular mechanisms against hepatocellular carcinoma (HCC) remain unclear. This study aims to elucidate the anti-HCC mechanisms of ZQ using chemical profiling, bioinformatics, Mendelian randomization (MR), and experimental validation. A total of 104 compounds were identified from ZQ, with 18 targeting HCC-related proteins. Bioinformatics and MR analyses revealed PTK2 as a core target associated with HCC risk. ZQ significantly suppressed H22 tumor growth in male ICR mice and inhibited PTK2/PI3K/AKT phosphorylation. Molecular docking and dynamics simulations confirmed stable binding between key ZQ compounds and PTK2. These results suggest that ZQ exerts anti-HCC effects through PTK2 inhibition and modulation of the PI3K/AKT pathway, supporting its potential as a multi-targeted therapeutic for HCC.