Arterial instillation of rapamycin in treatment of rabbit hepatic xenograft tumors and its effects on VEGF, iNOS, HIF-1α, Bcl-2, Bax expression and microvessel density

Tao Wu; Yihui Yao; Ruimin Sun; Huili Wang; Junna Zhang; Xiaoxiang Yin; Qing Zhou; Chaoshen Huangfu

doi:10.1177/00368504211026417

Arterial instillation of rapamycin in treatment of rabbit hepatic xenograft tumors and its effects on VEGF, iNOS, HIF-1α, Bcl-2, Bax expression and microvessel density

Sci Prog. 2021 Jul-Sep;104(3):368504211026417. doi: 10.1177/00368504211026417.

Authors

Tao Wu^{1

2}, Yihui Yao², Ruimin Sun¹, Huili Wang¹, Junna Zhang³, Xiaoxiang Yin², Qing Zhou², Chaoshen Huangfu⁴

Affiliations

¹ Department of Radiology Intervention, The First affiliated Hospital of Henan University of Traditional Chinese Medicine (TMC), Zhengzhou, Henan, P.R. China.
² Department of Radiology Intervention, The First Affiliated Hospital of Henan University, Kaifeng, Henan, P.R. China.
³ Department of Pathology, The First Affiliated Hospital of Henan University, Kaifeng, Henan, P.R. China.
⁴ College of Basic Medicine, Henan University, Kaifeng, Henan, P.R. China.

Abstract

Hepatocellular carcinoma is one of the leading causes of malignant tumor related death word wide with poor prognosis. Chemotherapy and TACE are main treatment methods for advanced stage cases. Rapamycin, a macrolide compound that initially used to coat coronary stents, can inhibit the growth of a variety of cancer cells especially hepatocellular carcinoma. Twenty-four healthy adult New Zealand white rabbits underwent CT-guided puncture to prepare a model of VX2 liver xenograft tumor. The rabbits were randomly divided into four groups with six in each group and received the following treatments: APR-TACE1: arterial perfusion of high-dose rapamycin combined with TACE; APR-TACE2: arterial perfusion of low-dose rapamycin combined with TACE; TACE: TACE alone; and IVR-TACE: intravenous injection of rapamycin combined with TACE. Two weeks after TACE treatment, the rabbits received CT scan and DSA angiography examination, and then killed by air embolism. The non-necrotic region and surrounding tissues were obtained from the peripheral tumor for iNOS, HIF-1α, VEGF, Bcl-2, and Bax protein expression analysis. Protein expression of iNOS, HIF-1α, VEGF, and Bcl-2 in APR-TACE1 were significantly lower than those in groups APR-TACE2, TACE, and IVR-TACE (p < 0.05). iNOS, HIF-1α, and VEGF in APR-TACE2 were lower than those in TACE (p < 0.05). iNOS and VEGF in APR-TACE2 were significantly lower than those in IVR-TACE (p < 0.05). iNOS in IVR-TACE was significantly lower than that in TACE (p < 0.05). The expression levels of Bcl-2 and Bax were statistically significant between APR-TACE2 and TACE (p < 0.05). The MVD of the tumor tissue in APR-TACE1 was lower than that of groups APR-TACE2, TACE, IVR-TACE with statistical difference (p < 0.05). However, MVD of APR-TACE2 was lower than that of groups TACE, IVR-TACE with significant statistical difference (p < 0.05). Arterial instillation of rapamycin+TACE in treatment of rabbit hepatic xenograft tumors can reduce tumor neovascularization and inhibit iNOS, HIF-1α, VEGF, Bcl-2, and Bax protein expression.

Keywords: Liver neoplasms; TCAE; hepatic xenograft tumor; rapamycin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Heterografts
Humans
Microvascular Density
Rabbits
Sirolimus* / pharmacology
Sirolimus* / therapeutic use
Vascular Endothelial Growth Factor A* / genetics
Vascular Endothelial Growth Factor A* / metabolism
bcl-2-Associated X Protein / genetics

Substances

bcl-2-Associated X Protein
Sirolimus
Vascular Endothelial Growth Factor A