Efficacy of transcatheter arterial chemoembolization combined with sorafenib in inhibiting tumor angiogenesis in a rabbit VX2 liver cancer model

WeiZhi Li; ShuZhen Kong; JingWen Su; Jin Huang; Hui Xue

doi:10.1016/j.jimed.2020.01.003

Efficacy of transcatheter arterial chemoembolization combined with sorafenib in inhibiting tumor angiogenesis in a rabbit VX2 liver cancer model

J Interv Med. 2020 Jan 21;3(1):27-33. doi: 10.1016/j.jimed.2020.01.003. eCollection 2020 Feb.

Authors

WeiZhi Li¹, ShuZhen Kong², JingWen Su¹, Jin Huang¹, Hui Xue¹

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
² Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, China.

Abstract

Background: The aim of this study was to investigate the effects of transcatheter arterial chemoembolization (TACE) combined with sorafenib on tumor angiogenesis.

Materials and methods: Thirty New Zealand rabbit VX2 liver cancer model animals were divided into five groups, which received either normal saline (A), TACE (B), sorafenib (C), sorafenib followed by TACE (D), or TACE followed by sorafenib (E). Serum vascular endothelial growth factor (VEGF) levels were measured before and after TACE via ELISA. Immunohistochemistry for CD34 was performed to evaluate microvessel density (MVD), and ultrasonography was used to access tumor volume.

Results: VEGF levels declined in group C but increased significantly on the 3rd post-operative day in groups B, D, and E. Levels decreased after the 7th post-operative day. Peak levels were significantly lower in group D than in groups B and E. On the 14th post-operative day, VEGF levels were the lowest in group C, followed by those in groups D and B. MVD was the lowest in group C followed by that in group D and E, and was the highest in group B. Group D had the smallest tumor volume. HE staining of tumor tissues from group C showed apoptosis in a scattered patchy pattern, whereas in groups B, D, and E, large areas of tumor cell necrosis were visible.

Conclusion: TACE can up-regulate serum VEGF levels, which in turn accelerates the formation of new blood vessels. Thus, TACE combined with sorafenib inhibits VEGF and angiogenesis, and pre-operative administration of sorafenib has a more superior anti-angiogenic effect than post-operative administration.

Keywords: Hepatocellular carcinoma; Microvessel density (MVD); Sorafenib; Transcatheter arterial chemoembolization (TACE); Vascular endothelial growth factor (VEGF).