Yoshizawa J, Mizuno R, Yoshida T, Hara A, Ashizuka S, Kanai M, Kuwashima N, Kurobe M, Yamazaki Y
Department of Surgery, Division of Pediatric Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
J Surg Res. 2000 Sep;93(1):82-7. doi: 10.1006/jsre.2000.5956.
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.
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.
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).
TNP-470 inhibits metastasis of mouse C1300 neuroblastoma cells to the liver, and thus increases survival. TNP-470 inhibits metastasis by inhibiting angiogenesis.
TNP - 470是一种强效血管生成抑制剂。本研究旨在确定血管生成抑制剂TNP - 470是否能抑制小鼠神经母细胞瘤细胞向肝脏的转移，从而提高生存率。
本研究使用了一种小鼠神经母细胞瘤细胞系C1300和A/J小鼠。首先，为了证明TNP - 470对血管生成的抑制作用，我们在植入微孔小室7天后，使用SP - 500图像分析仪（奥林巴斯）对图像上的血管生成区域进行量化，并比较TNP - 470处理组小鼠和对照组小鼠的血管生成区域。接下来，为了确定TNP - 470对神经母细胞瘤细胞向肝脏转移的抑制作用，我们通过将C1300细胞（1×10⁶个）植入小鼠脾脏建立了小鼠肝转移模型，并比较在开始7天输注TNP - 470（60mg/kg）14天后处理组小鼠和对照组小鼠肝脏的组织学表现、大小和重量。我们还使用Kaplan - Meier方法比较生存率。
当将血管生成抑制剂TNP - 470注入接种了肿瘤细胞的小鼠体内时，TNP - 470处理组小鼠的血管生成区域小于对照组小鼠（52.5±6.3标准差 vs 94.1±27.6mm²，P < 0.001）。在对其他小鼠进行相同处理后，未发现转移的组织学证据，而对照组小鼠有无数肿瘤细胞团块。同样，TNP - 470处理组小鼠的肝脏重量较轻（0.8±0.1g vs 4.5±0.3g，P < 0.001）。TNP - 470处理组小鼠的生存期比对照组小鼠长（80%的处理组小鼠在治疗后60多天仍存活，而所有对照组小鼠在第20天死亡）。
TNP - 470抑制小鼠C1300神经母细胞瘤细胞向肝脏的转移，从而提高生存率。TNP - 470通过抑制血管生成来抑制转移。
