血管生成抑制对小鼠颌下区肉瘤生长的影响

TNP-40 inhibits the growth of submandibular sarcoma in KM mice

目的 :建立小鼠颌下区肉瘤模型 ,探讨血管生成抑制剂TNP 470对颌下区肉瘤形成及生长的影响。方法 :将S 180细胞接种于小鼠一侧颌下区 ,接种量每 0 1ml含 1× 10 6。随机将 40只小鼠分为 4组 ,每组 10只 ,雌雄各半。即对照组、TNP 470 ( 10mg/kg)、TNP 470 ( 3 0mg/kg)、TNP 470 ( 10 0mg/kg)治疗组。接种后8h起远离肿瘤区皮下注射给药 ,对照组给相应溶剂。隔天给药 1次 ,共 6次。接种后第 12天处死小鼠 ,解剖出瘤体并称重 (鼠及肿瘤 )。各组间瘤称重、鼠称重作方差分析。免疫组化染色检测各组VEGF、bFGF表达。TUNEL法、透射电镜观察各组凋亡情况。结果 :移植瘤生长迅速 ,侵袭性强 ,肿瘤灶边界不清可浸润局部肌肉 ,侵犯颌下腺、腮腺、面神经。S 180肉瘤可通过表达VEGF、bFGF促进瘤体血管生成。TNP 470对颌面区肉瘤有较好的生长抑制效果 ,并呈剂量依赖性。TNP 470通过抑制血管生成 ,减少瘤体血供 ,诱导S 180肉瘤细胞凋亡 ,抑制肿瘤增殖 ,剂量与凋亡数之间呈正相关。结论 :血管生成抑制可望成为治疗颌面部肉瘤的新途径。

Objective: To study the effect of a potent angiogenic in hi bitor TNP-470 on the growth of sarcoma. Methods:1×10 6 sarcom a S-180 cells 0.1 ml were inoculated into submandibular region in each of 40 K M mice. The mice were divided into control and treatment groups with 10 in each group. Treatment was started 8 hours after inoculation. TNP-40 at 10 mg/kg, 30 mg/kg and 100 mg/kg was given subcutaneously every other day in the 3 treatment groups,total 6 times. On the 12th day, the mice were sacrificed, tumor and mice were weighted. Apoptosis of tumor cells was observed by TUNEL method and transmi ssion microscope. Express of VEGF, bFGF were detected by immunohistochemical sta ining. Results:Sarcoma was developed in all of the mice. The sa rcoma cells invaded deep into adjacent organs and tissues such as muscle, subman dibular gland, parotid and facial nerve. 10 mg/kg, 30 mg/kg and 100 mg/kg TNP- 470 inhibited the growth of the tumor by 27.62%,63.81% and 85.71% respective ly, increased the apoptosis cell number by 54.46%,156.69% and 432.48% respect ively (P<0.05). TNP-470 did not inhibit the expression of VEGF and bFGF. Conclusion:Angiogenesis inhibitor TNP-470 may efficiently inhibit e sarcoma growth.