Griscelli F, Li H, Cheong C, Opolon P, Bennaceur-Griscelli A, Vassal G, Soria J, Soria C, Lu H, Perricaudet M, Yeh P
Le Centre National de la Recherche Scientifique Unité Mixte de Recherche 1582/Rhône-Poulenc Gencell, Institut Gustave Roussy, 94805 Villejuif, France.
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6698-703. doi: 10.1073/pnas.110134297.
The objective of the present study was to evaluate the antitumor effect of a defective adenovirus expressing a secretable angiostatin-like molecule (AdK3) in combination with radiotherapy in rat C6 gliomas s.c. preestablished into athymic mice. In vitro, the combination regimen was significantly (P < 0.001) more cytotoxic for human microcapillary endothelial cells than either treatment alone, whereas survival of C6 glioma cells was not affected in the conditions used. Radiotherapy and AdK3 gene delivery was then studied on well established C6 xenografts (165 +/- 70 mm(3)). In these tumors, AdK3 intratumoral injections had only a marginal effect. Interestingly, when experimental radiotherapy was added, significantly higher (P < 0.005), and possibly synergistic, antitumoral effects were observed that tightly correlated a marked decrease of intratumoral vascularization. The combination of radiotherapy and AdK3 intratumoral injections also revealed a significant (P < 0.05) inhibition of tumor growth as compared with either treatment alone for larger tumors (467 +/- 120 mm(3)). Altogether, these data emphasize the potential of combining a destructive strategy directed against the tumor cells with an anti-angiogenic approach to fight cancer.
本研究的目的是评估表达可分泌血管抑素样分子的缺陷型腺病毒（AdK3）与放疗联合应用对预先接种于裸鼠皮下的大鼠C6胶质瘤的抗肿瘤作用。在体外，联合治疗方案对人微血管内皮细胞的细胞毒性显著高于单独使用任何一种治疗方法（P < 0.001），而在所用条件下C6胶质瘤细胞的存活不受影响。随后，对已形成的C6异种移植瘤（165 +/- 70 mm(3)）进行放疗和AdK3基因递送研究。在这些肿瘤中，瘤内注射AdK3仅产生微小效应。有趣的是，当加入实验性放疗时，观察到显著更高（P < 0.005）且可能具有协同作用的抗肿瘤效应，这与瘤内血管生成的显著减少密切相关。与单独使用任何一种治疗方法相比，对于较大的肿瘤（467 +/- 120 mm(3)），放疗与瘤内注射AdK3的联合应用也显示出对肿瘤生长的显著抑制（P < 0.05）。总之，这些数据强调了将针对肿瘤细胞的破坏策略与抗血管生成方法相结合对抗癌症的潜力。
