重组人VEGF_(121KDR)/rGEL融合毒素抗肿瘤药效学研究

Anti-cancer effect of rhVEGF_(121KDR)/rGEL fusion toxin

目的：建立荷瘤小鼠模型，观察重组人VEGF121，xoR／rGEL融合毒素的抑瘤作用，为开发更加安全和有效的新型靶向抗癌药奠定基础。方法：选择人肝癌SMM-7721细胞、食管癌KYS-150细胞、胃癌sGC_7901和结肠癌HT-29细胞建立荷瘤小鼠模型；给药后每2-3d测量肿瘤大小，绘制肿瘤生长曲线，计算给药组相对肿瘤增长率。结果：在肝癌、食管癌、胃癌和结肠癌4种裸鼠移植瘤模型中，给药组肿瘤增长明显减慢，给药组肝癌裸鼠肿瘤体积为（89．33士56．36）mm^3，食管癌为（142．47±58．67）mm^3，胃癌为（73．80±31．05）mm^3，结肠癌为（79．64土34．46）mm^3；对照组肝癌为（328．19±200．27）mm^3，食管癌为（474．05±167．42）mm^3，胃癌为（172．34±41．78）mm^3，结肠癌为（480．26±348．34）mm^3。相对肿瘤体积给药组肝癌为5．31±2．13，食管癌为5．72±2．45，胃癌为3．59土1．55，结肠癌为5．82士1．92；对照组肝癌为17．10土6．00，食管癌为23．71士10．36，胃癌为11．65±4．14，结肠癌为23．24±5．74。相对肿瘤增殖率肝癌为31．05％，食管癌为24．12％，胃癌为25．04％，结肠癌为30．82％。给药组肿瘤体积和相对肿瘤体积均显著小于对照组，P值均d0．01。结论：重组人VEGF12KDR/rGEL融合毒素显著抑制多种肿瘤生长，可能是一种具有临床应用前景的候选靶向抗癌药。

OBJECTIVE： To investigate the anti-cancer effects and the tumor- targeting of rhVEGFtzmDR/rGEL fu- sion toxin in human tumor xenografts models for the development of more effective and safer anticancer drugs. METH- ODS：Human carcinoma xenografts models of hepatoma SMMC-7721 ceils, esophageal carcinoma KYSE-150 cells,Gastric carcinoma SGC-7901 cells and colon carcinoma HT-29 cells were established, Measuring tumor volume every 2--3 days af- ter administration,drawing tumor growth curve, and calculating the relative tumor growth rate. The localization of fusion toxin in tumor tissues were examined by immunohistochemistry. RESULTS： The volume of human carcinoma xenografts of SMMC-7721, KYSE-150,SGC-7901 and HT-29 was respectively （89.33±56.36） mm^3 , （142.47±58.67） mm^3 , （73.80±31.05） mm3 and （79. 64±34. 46） .ram^3 in the treated group, and （328. 19±200. 27） mm^3, （474. 05±167. 42） mm^3, （172.34±41.78） mm^3 and （480. 26±348.34） mm^3 in the untreated group. The relative tumor volume（ RTV） of the four human carcinoma xenografts in the treated group was respectively 5.31±2.13, 5.72±2.45, 3.59±1.55 and 5.82±1.92,and in un- treated group, the RTV was respectively 17.10±6.00, 23.71±10.36,11.65±4.14 and 23.24±5.74. The relative growth rate was respectively 31.05%, 24.12%, 25.04% and 30. 820/oo. Both tumor volume and RTV of human carcinoma xenogrMts treated with the fusion toxin demonstrated significant reduction compared with untreated controls （all P〈0.01）. CONCLUSION： The rhVEGFlzlKDR/rGEL can significantly inhibit tumor growth in at least four xenograft models, and is a promising candidate drug for the targeted therapy of cancer.