Effects of Tetrahydrocurcumin on Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor Expression in Cervical Cancer Cell-Induced Angiogenesis in Nude Mice

Abstract EN

Tetrahydrocurcumin (THC), one of the important in vivo metabolites of curcumin, inhibits tumor angiogenesis.

Its effects on angiogenesis in cervical cancer- (CaSki-) implanted nude mice and its mechanisms on hypoxia-inducible factor-1α and vascular endothelial growth factor expression were investigated.

Female BALB/c nude mice were divided into control (CON) and CaSki-implanted groups (CaSki group).

One month after the injection with cervical cancer cells, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days.

The microvascular density (MVD) was evaluated using the CD31 expression.

VEGF, VEGFR-2, and HIF-1α expression were also detected by immunohistochemistry.

The MVD in CaSki + vehicle group was significantly increased compared to the CON + vehicle group.

Interestingly, when treated with THC at all doses, the CaSki group showed a significant smaller number of the MVD.

The CaSki + vehicle group also showed significantly increased VEGF, VEGFR-2, and HIF-1α expressions, but they were downregulated when mice were treated with THC at all doses.

THC demonstrated an inhibitory effect against tumor angiogenesis in CaSki-implanted nude mice model.

This effect is likely to be mediated by the downregulation of HIF-1-α, VEGF expression, and its receptor.

THC could be developed into a promising agent for cancer therapy in the future.