1. Academic Validation
  2. Blocking transforming growth factor-beta reduces the migration and invasion of the residual tumour after TAE

Blocking transforming growth factor-beta reduces the migration and invasion of the residual tumour after TAE

  • Am J Transl Res. 2019 Apr 15;11(4):2155-2167.
Songlin Song 1 Xiaojun He 1 2 Zhuanglin Zeng 3 Hongsen Zhang 1 Qi Yao 1 Fan Yang 1 Chuansheng Zheng 1 Xiaopeng Guo 1
Affiliations

Affiliations

  • 1 Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, Hubei, China.
  • 2 Department of Radiology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology Wuhan 430016, Hubei, China.
  • 3 Department of Emergency Internal Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, Hubei, China.
PMID: 31105825
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.

Keywords

TGF-β/Smad pathway; Transarterial embolization (TAE); tumour microenvironment.

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