血管生成抑制剂TNP-470与细胞毒药物Gem citabine的抗胰腺癌生长和转移作用的比较研究

Comparative study of the inhibitory effect of angiogenesis inhibitor, TNP-470 and Gemcitabine on the growth and metastasis of pancreatic carcinoma

目的 探讨血管生成抑制剂 (TNP- 4 70 )和细胞毒药物 (Gemcitabine)对胰腺癌裸鼠原位移植模型 (SOI)生长、转移的抑制作用及其作用机制。方法 把胰腺癌细胞株 SW1990皮下种植生长的癌组织移植于裸鼠胰腺尾部 ,制备胰腺癌 SOI模型 ;2 4只 SOI模型随机分为 TNP组 (TNP- 4 70 30 m g/ kg,皮下注射 ,隔日一次 ,疗程 8周 )、GEM组 (Gemcitabine 10 0 mg/ kg,腹腔内注射 ,术后第 0、3、6、9天给药 )和对照组 ,术后第 10周处死裸鼠。结果 Gemcitabine侧重于抗胰腺癌生长 ,TNP- 4 70则侧重抑制胰腺癌转移 ,两者均无显著的预后改善作用 ;TNP组的微血管密度 (MVD)显著低于 GEM组和对照组 ,GEM组的肿瘤增殖指数 (PI)显著低于 TNP组和对照组 (均 P<0 .0 5 )。结论 血管生成抑制剂和细胞毒药物在抗肿瘤生长和转移的侧重点和作用机制方面均存在显著差异。

Objective The anti-tumor and anti-metastasis effects of TNP-470, an angiogenesis inhibitor, and Gemcitabine, a representative cytotoxic drug, were investigated using an SOI model of human pancreatic carcinoma. Methods The SOI model was developed by suturing small pieces of SW1990 tumors into the tail of pancreas in nude mice. Twenty-four male mice were randomly divided into control group, GEM group receiving Gemcitabine 100 mg/kg i.p. on day 0, 3, 6 and 9 after transplantation, and TNP group receiving TNP-470 30 mg/kg s.c. on every other days for 8 weeks. Animals were killed at the tenth week after transplantation. Results Gemcitabine had a significant inhibitory effect on primary tumor growth of pancreatic carcinoma compared to TNP-470, while the metastasis of tumor was significantly inhibited by TNP-470 compared to Gemcitabine. Neither Gemcitabine nor TNP-470 showed a significant improvement on the survival rate. The level of microvessel density (MVD) in TNP group was significantly lower than that in GEM group and control group, while the level of proliferative indices (PI) in GEM group was significantly lower than that in TNP group and control group (P < 0.05). Conclusions There seem to be differences in anti-tumor and anti-metastatic effect and actions between angiogenesis inhibitor and cytotoxic drugs.