Octreotide and celecoxib synergistically encapsulate VX2 hepatic allografts following transcatheter arterial embolisation

Abstract

To evaluate the encapsulation of VX2 hepatic allografts in rabbits induced by octreotide and celecoxib administration following transcatheter arterial embolisation (TAE), rabbits with hepatic VX2 allografts were divided into four groups: control, TAE, octreotide + celecoxib (O+C) and the multimodality therapy (TAE+O+C). Allograft metastasis, capsule thickness and percentage of clear cells were measured and vascular endothelial growth factor (VEGF) and CD31 were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis. The extrahepatic metastases of each intervention group were significantly fewer than those of the control group, with the TAE+O+C group exhibiting the fewest extrahepatic metastases. The TAE+O+C group had the greatest proportion of clear cells and thickest capsule on day 30. Increased capsule thickness was negatively correlated with tumour metastasis. In addition, VEGF expression levels assessed by immunohistochemistry and RT-PCR in the three intervention groups were significantly lower than those in the control group. Furthermore, the TAE+O+C group had a significantly reduced CD31 count induced by TAE. These results demonstrate that TAE, followed by long-term administration of octreotide and celecoxib, synergistically inhibits VX2 hepatic allograft metastasis by increasing the proportion of clear cells, promoting encapsulation and inhibiting angiogenesis.

Adjuvant celecoxib and lanreotide following transarterial chemoembolisation for unresectable hepatocellular carcinoma: a randomized pilot study

“…Such a synergistic inhibitory role in HCC treatment is supported by the basis of our previous experiment of rabbits with hepatic VX2 allografts. In the animal model, TACE plus octreotide and celecoxib synergistically prolonged the survival through antiangiogenesis, induction of allograft capsule formation, and inhibition of growth and metastasis of the tumour [ 16 , 17 ]. Although protocol of either TACE+lanreotide/octreotide or TACE+celecoxib ever showed a little survival benefit in our previous animal experiment or preclinical test, their efficacies were inferior to that of TACE+lanreotide/octreotide+celecoxib.…”

“…Recently, we observed that pasireotide, combined with celecoxib, prolonged the survival in nude mice [ 15 ]. Moreover, combination of the above two types of non-cytotoxic agents displayed a synergistic inhibitory role on the growth or metastasis of the liver neoplasm in rabbits of post-TACE [ 16 , 17 ]. However, the potential effects of the multi-modality protocol on the survival of patients who underwent TACE have not been assessed.…”

Modification of the method to establish a hepatic VX2 carcinoma model in rabbits

“…Previous studies have demonstrated that the majority of rabbits underwent metastasis ~40 days after tumor implantation (8,14). Distal metastasis and abdominal implantation occurring at a late stage of liver carcinoma were usually accompanied by either intrahepatic metastasis or large primary implantation foci (8).…”

Antitumoral and Anti-inflammatory Roles of Somatostatin and Its Analogs in Hepatocellular Carcinoma

“…The combination of a COX 2 inhibitor with SSAs demonstrated antiproliferative effects [ 98 ], a combination also proving successful in rabbits [ 97 ]. Following transcatheter arterial embolization, a combination treatment of octreotide with celecoxib also inhibited metastasis and angiogenesis [ 122 ]. A recent experiment on Sprague-Dawley rats has also raised the possibility of using octreotide preventatively in nonalcoholic steatosis, to prevent HCC development [ 123 ].…”