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Published on: April 15, 2016
Intra-arterial administration of the angiogenesis inhibitor TNP-470 blocks liver metastasis in a rabbit model
H Tanaka1, H Taniguchi, T Mugitani
1First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Abstract:
We evaluated the best route of administration of TNP-470, an angiogenesis inhibitor, by comparing the anti-tumour effects and toxicity following injection via the hepatic artery, the portal vein, or the jugular vein in a rabbit model of liver metastases. Following the injections of 1 x 10(6) VX2 carcinoma cells into the portal vein of rabbits, 50 mg of TNP-470 was injected continuously into the hepatic artery, portal vein, or jugular vein for 7 days. The number of tumours on the surface of the liver was counted 14 days following the start of the infusion, and the serum glutamic-oxaloacetic transamine (GOT), glutamic-pyruvic transaminase (GPT) and total bilirubin concentrations were examined. In addition, a coloured silicon rubber was injected into the vessels of the liver to visualise the capillary networks around the tumours and assess the degree of suppression of angiogenesis by TNP-470. The mean number of tumours following intra-arterial injection (17.5 +/- 2.9) was significantly less than the control (237.0 +/- 34.0) (P < 0.05). The mean numbers of the tumours following intraportal (89.1 +/- 16.0) and intravenous (140.6 +/- 31.2) injection were both less than the controls (215.3 +/- 45.5, 284.8 +/- 55.4 respectively), but the differences were not significant. We conclude that intra-arterial injection of TNP-470 is the most effective method for preventing liver metastases in this model.
Insights
Intra-arterial administration of TNP-470, an angiogenesis inhibitor, significantly reduced liver tumors in rabbits. This route proved most effective in preventing liver metastases compared to other injection methods.
Area of Science:
- Oncology
- Pharmacology
- Vascular Biology
Background:
- Liver metastases represent a significant clinical challenge.
- Angiogenesis inhibitors are a promising therapeutic strategy.
- TNP-470 is a potent inhibitor of angiogenesis.
Purpose of the Study:
- To determine the optimal route of administration for TNP-470 in treating liver metastases.
- To compare the anti-tumour efficacy and toxicity of TNP-470 via hepatic artery, portal vein, and jugular vein injections.
- To evaluate the impact of TNP-470 on angiogenesis in a rabbit liver metastasis model.
Main Methods:
- VX2 carcinoma cells were injected into the portal vein of rabbits to establish liver metastases.
- TNP-470 (50 mg) was administered continuously for 7 days via hepatic artery, portal vein, or jugular vein.
- Tumour burden, liver enzyme levels (GOT, GPT), bilirubin, and tumour vascularity were assessed.
Main Results:
- Intra-arterial TNP-470 injection resulted in a significant reduction in liver tumour number (17.5 ± 2.9) compared to controls (237.0 ± 34.0, P < 0.05).
- Intraportal and intravenous administration showed reduced tumour counts but without statistical significance.
- Visualisation of liver vasculature indicated TNP-470 suppressed tumour angiogenesis.
Conclusions:
- Intra-arterial administration of TNP-470 is the most effective route for inhibiting liver metastases in this rabbit model.
- This delivery method demonstrates superior anti-tumour activity and potential for managing liver cancer progression.
- Further investigation into TNP-470's therapeutic potential via intra-arterial delivery is warranted.
