Abstract
This study aimed to investigate the treatment effects of combining TAE therapy with LY2109761, a transforming growth factor-beta (TGF-β) receptor I kinase inhibitor, on suppressing tumour growth and metastasis. We simulated the changing tumour microenvironment before and after TAE using both in vitro and in vivo models. In vitro, we evaluated the altered migration and invasion properties of HepG2 cells using migration and invasion assays. In addition, western blot analysis was used to investigate molecular mechanisms underlying the biological activities of LY2109761 in HepG2 cells. In vivo, we combined LY2109761 with TAE together in the VX2 rabbit model to evaluate the therapeutic effects of the combination. In vitro, the Smad pathway were substantially activated by hypoxia, and LY2109761 significantly inhibited the Smad pathway under both normoxic and hypoxic circumstances. Furthermore, LY2109761 inhibited cell proliferation, intravasation and metastasis by downregulating Smad-2 phosphorylation and up-regulating E-cadherin expression in both normoxic and hypoxic conditions. In addition, in animals, LY2109761 improved the therapeutic effect of TAE and inhibited intravasation and metastasis after TAE. Based on the observations herein, we concluded that using LY2109761 and TAE in combination for the treatment of VX2 rabbit liver cancer inhibits tumour growth and metastasis, suggesting that such a combination may provide new a target and strategy for interventional liver cancer therapy.