Tanshinone IIA-based imidazole compounds exert dual anti-angiogenic and anti-tumor effects in hepatocellular carcinoma by modulating VEGFR2.

Authors

Zhifang Lai, Qingyou Pan, Xiaozhan Qiu, Jiangbo Liang, Peiyao Huang, Bin Zhao, Jinlan Meng, Wenjie Mei

Published in

The international journal of biochemistry & cell biology. Pages 107034. Sep 28, 2026. Epub Sep 28, 2026.

Abstract

Tanshinone IIA, a bioactive lipophilic diterpenoid from Salvia miltiorrhiza Bunge (Lamiaceae), exhibits anti-tumor effects but is limited by poor pharmacokinetic properties. Building on our previously reported tanshinone IIA-derived imidazole analogue (1), we systematically evaluated its anti-hepatocellular carcinoma (HCC) activity and investigated its effects on VEGFR2 signaling in relation to autophagy. In vitro, compound 1 inhibited HepG2 colony formation and migration while inducing minimal apoptosis. Immunofluorescence revealed altered paxillin distribution and reduced FAK expression. In VEGF-induced and tumor-induced angiogenesis models using transgenic zebrafish (Tg-fli1a: EGFP), compound 1 suppressed ectopic vessel sprouting and reduced HepG2 xenograft growth. Notably, compound 1 treatment dose-dependently suppressed VEGFR2 phosphorylation without altering total VEGFR2 expression in both HepG2 cells and VEGF-stimulated endothelial cells. Concurrently, compound 1 induced autophagic features (LC3-II accumulation and autolysosome formation) and downregulated the PI3K/AKT/mTOR pathway. These findings indicate that compound 1 exerts dual anti-angiogenic and anti-tumor effects in HCC, with VEGFR2 phosphorylation inhibition as a key contributing pathway.

PMID:
42805401
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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