TNP-470联合顺铂抗腺样囊性癌生长和肺转移的实验研究

The Inhibitory Study of TNP-470 Combined CDDP on the Tumor Growth and Lung Metastasis of Adenoid Cystic Carcinoma ACC M in Nude Mice

目的 研究血管生成抑制剂TNP 470联合顺铂 (CDDP)对口腔腺样囊性癌生长及肺转移的抑制作用。方法 分别将建株的口腔腺样囊性癌肺转移细胞株 (ACC M)细胞悬液注射至裸鼠皮下和尾静脉 ,建立口腔腺样囊性癌皮下移植瘤及实验性肺转移模型。从移植后的第 3周开始 ,于裸鼠对侧皮下注射TNP 470 30mg/kg,隔日 1次 ,共7次。CDDP分别在第 3周和第 4周腹腔给药各 1次 ,剂量为 5mg/kg。停药后第 2d处死裸鼠。测量肿瘤大小 ,称重并计数肺转移结节数。以兔抗人Ⅷ因子相关抗原抗体免疫组化染色后 ,计数皮下瘤块血管密度。结果 与单用TNP 470相比 ,TNP 470联合CDDP对口腔腺样囊性癌生长和肺转移的抑制作用更强 ,但对皮下移植瘤的血管密度影响无明显差异。结论 TNP 470联合CDDP对口腔腺样囊性癌生长和肺转移有明显的抑制作用。

Objective To study the effect of TNP 470 combined CDDP on the tumor growth and lung metastasis of cell strain ACC M in vivo. Methods High potential lung metastatic adenoid cystic carcinoma cell strains (ACC M) 5×10 5 were injected simultaneously to 18 nude mice subcutaneously and venously. The animals were randomly divided into 3 groups. In group 1, TNP 470 was administered subcutaneously at the dose of 30mg/kg every other day for 2 weeks from the beginning of 3 rd week to the end of 4 th week. In group 2, 5mg/kg CDDP were injected into peritoneal cavity at the beginning of 3 rd week and 4 th week and TNP 470 in the same manner as group 1 additionally. In group 3, the same volume of 0.9%NaCl was injected in the manner of group 1. The mice were sacrificed by dislocating the neck at the end of 4 weeks. The tumor size and weights were recorded. The vascular density was measured by rabbit anti human factor Ⅷ antibody stain. The results were analyzed by Student t and χ 2 test. Results Group 1 and group 2 had fewer tumor weight and lung metastasis than the 3 rd group. There was significant difference in the tumor weight and lung metastasis between group 1 and group 2. But the vascular density had no difference among three groups. Conclusion TNP 470 combined CDDP has stronger inhibition on both the tumor growth and lung metastasis of human adenoid cystic carcinoma ACC M than used alone.