原发瘤切除对荷人骨肉瘤裸鼠血管生成和肺转移的影响

目的 研究原发瘤切除对骨肉瘤血管生成和肺转移的影响,并探讨其可能的机制及临床意义.方法 用细胞悬液法构建倚人骨肉瘤裸鼠模型,分为实验组(切除原发瘤)、截肢对照组(不切除原发瘤的截肢手术)和空白对照组.用酶联免疫吸附试验(ELISA)法,检测手术前后裸鼠血清中血管内皮生长因子(VEGF)和内皮抑素的表达水平.用HiCN法检测裸鼠体内Matrigel胶体中血红蛋白浓度.应用膨胀压片计数法和组织切片苏木素-伊红对比染色法,观察肿瘤肺部转移灶的情况.结果 手术后实验组血清中的VEGF和内皮抑素浓度较空白对照组和截肢对照组有明显的下降,且内皮抑素下降幅度更大VEGF分别为(71.43±9.15)pg/ml、(115.81±4.38)pg/ml和(111.68±12.26)ps/ml(P<0.01);内皮抑素分别为(40.77±5.41)ng/ml、(123.18±5.94)ng/ml和(128.06±4.52)ng/ml(P<0.01)];实验组、空白对照组和截肢对照组Matrigel小体中血红蛋白浓度分别为(36.55±2.35)g/L、(16.84±1.15)g/L和(16.29±1.10)g/L(P<0.01).实验组、空白对照组和截肢对照组的肺转移率分别为80.0%、40.0%和35.0%,差异有统计学意义(P<0.05).结论 原发瘤切除可使荷人骨肉瘤裸鼠体内的VEGF和内皮抑素比例失衡,有利于肿瘤血管生成和肺转移,故原发瘤切除后及时抑制肿瘤血管生成,对降低骨肉瘤肺转移有重要意义.

Effects of primary tumor excision on angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice

Objective To investigate the effects of primary tumor excision on osteosareoma angiogenesis and pulmonary metastasis, and explore its possible mechanism and clinical significance. Methods The tumor-bearing nude mice were constructed by injection of human osteosarcoma cell suspension, and divided into primary tumor resection, amputaion and normal groups. The level of VEGF and endostatin was examined by ELISA assay. The hemoglobin content in Matrigel pellets was measured with HiCN method. Pulmonary metastasis was detected with dilated-squash technique and immunohistochemical staining. Results The serum VEGF and endostatin level was significantly decreased in the primary tumor excision group compared with that in the normal and control groups after operation, but endostatin decreased more prominently VEGF: (71.43±9.15 ) pg/ml vs. ( 115.81±4.38 ) pg/ml, (111.68±12.26) pg/ml, P<0.01; ES:(40.77±5.41)ng/ml vs. (123.18±5.94)ng/ml, (128.06±4.52)ng/ml, P<0.01]. The HB contents in Matrigel pellets increased in the primary tumor excision group compared with that in normal and control groups (36.55±2.35) g/L vs. (16.84±1.15) g/L, (16.29±1.10) g/L, P<0.01]. The rate of pulmonary metastasis in tumor excision group was much higher than that in the un-excised groups (80.0% vs. 40.0% and 35.0%, P<0.05). Conclusion The excision of primary tumor can promote osteosarcoma angiogenesis and pulmonary metastasis, so anti-angiogenic treatment after operation has instructive clinical significance in preventing tumor metastasis.