Related Experiment Videos
Inhibitory effect of TNP-470 on hepatic metastasis of mouse neuroblastoma
J Yoshizawa1, R Mizuno, T Yoshida
1Department of Surgery, Division of Pediatric Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Purpose:
TNP-470 is a strong inhibitor of angiogenesis. The present study was designed to determine whether the angiogenesis inhibitor TNP-470 inhibits metastasis of mouse neuroblastoma cells to the liver and thus increases survival.
Methods:
A murine neuroblastoma cell line, C1300, and A/J mice were used in this study. First, to demonstrate the inhibitory effects of TNP-470 on angiogenesis, we quantified the area of angiogenesis on images made with SP-500 image analyzer (Olympus) 7 days after implanting a millipore chamber and compared the areas for the TNP-470-treated mice and control mice. Next, to determine the inhibitory effect of TNP-470 on metastasis of neuroblastoma cells to the liver, we made a murine hepatic metastasis model by implanting C1300 cells (1 x 10(6)) in the spleen of the mice and compared histologic findings, sizes, and weights of the livers of treated mice and control mice 14 days after the beginning of a 7-day infusion of TNP-470 (60 mg/kg). We also compared survival rates using the Kaplan-Meier method.
Results:
When the angiogenesis inhibitor TNP-470 was infused into mice that received tumor cells, the area of angiogenesis in the TNP-470-treated mice was smaller than that in the control mice (52.5 +/- 6.3 SD vs 94.1 +/- 27.6 mm(2), P < 0.001). After the same treatment in other mice, no histologic evidence of metastasis was found, whereas control mice had countless tumor cell masses. Similarly, the weight of the liver was less in TNP-470-treated mice (0.8 +/- 0.1 g vs 4.5 +/- 0.3 g, P < 0.001). Survival was longer in the TNP-470-treated mice than in controls (80% of treated mice were alive more than 60 days after treatment, whereas all control mice died by Day 20).
Conclusion:
TNP-470 inhibits metastasis of mouse C1300 neuroblastoma cells to the liver, and thus increases survival. TNP-470 inhibits metastasis by inhibiting angiogenesis.
Insights
The angiogenesis inhibitor TNP-470 effectively reduced neuroblastoma liver metastasis in mice. This inhibition of angiogenesis led to increased survival rates, demonstrating TNP-470
Area of Science:
- Oncology
- Angiogenesis Research
- Translational Medicine
Background:
- Angiogenesis is crucial for tumor growth and metastasis.
- Neuroblastoma is a pediatric cancer with a high metastatic potential.
- TNP-470 is a potent inhibitor of angiogenesis.
Purpose of the Study:
- To investigate the efficacy of TNP-470 in inhibiting neuroblastoma metastasis to the liver.
- To determine if TNP-470 can improve survival rates in a murine model of neuroblastoma.
Main Methods:
- A murine neuroblastoma cell line (C1300) was used in A/J mice.
- Angiogenesis was quantified after TNP-470 treatment.
- A hepatic metastasis model was established by splenic injection of neuroblastoma cells.
- Histological analysis, liver weight, and survival rates were compared between TNP-470 treated and control groups.
Main Results:
- TNP-470 significantly reduced the area of angiogenesis compared to controls (52.5 vs 94.1 mm²).
- No liver metastasis was observed in TNP-470 treated mice, while controls showed extensive tumor masses.
- Liver weight was significantly lower in treated mice (0.8 vs 4.5 g).
- Survival was markedly improved, with 80% of treated mice alive after 60 days versus all controls dying by day 20.
Conclusions:
- TNP-470 effectively inhibits the metastasis of C1300 neuroblastoma cells to the liver in mice.
- The anti-metastatic effect of TNP-470 is attributed to its ability to inhibit angiogenesis.
- TNP-470 demonstrates potential as a therapeutic agent for increasing survival in neuroblastoma.