Curcumin Suppresses Hepatic Stellate Cell-Induced Hepatocarcinoma Angiogenesis and Invasion through Downregulating CTGF

Abstract EN

Microenvironment plays a vital role in tumor progression; we focused on elucidating the role of hepatic stellate cells (HSCs) in hepatocarcinoma (HCC) aggressiveness and investigated the potential protective effect of curcumin on HSC-driven hepatocarcinoma angiogenesis and invasion.

Our data suggest that HSCs increase HCC reactive oxygen species (ROS) production to upregulate hypoxia-inducible factor-1α (HIF-1α) expression to promote angiogenesis, epithelial to mesenchymal transition (EMT) process and invasion.

And HSCs could secrete soluble factors, such as interleukin-6 (IL-6), vascular endothelial cell growth factor (VEGF), and stromal-derived factor-1 (SDF-1) to facilitate HCC progression.

Curcumin could significantly suppress the above HSC-induced effects in HCC and could abrogate ROS and HIF-1α expression in HCC.

HIF-1α or connective tissue growth factor (CTGF) knockdown could abolish the aforementioned curcumin affection.

Moreover, CTGF is a downstream gene of HIF-1α.

In addition, nuclear factor E2-related factor 2 (Nrf2) and glutathione (GSH) are involved in curcumin protection of HCC.

These data indicate that curcumin may induce ROS scavenging by upregulating Nrf2 and GSH, thus inhibiting HIF-1α stabilization to suppress CTGF expression to exhibit its protection on HCC.

Curcumin has a promising therapeutic effect on HCC.

CTGF is responsible for curcumin-induced protection in HCC.