Combined effects of soluble vascular endothelial growth factor receptor FLT-1 gene therapy and cisplatin chemotherapy in human tongue carcinoma xenografts.
The aim of the present study was to assess the anti-tumor effect of a defective adenovirus that expresses soluble vascular endothelial growth factor (VEGF) receptor FLT-1 (AdsFLT-1) in combination with cisplatin (cis-diamminedichloroplatinum, DDP) on human tongue carcinoma Tca8113 cell xenografts that had been pre-established in nude mice. In vitro, Tca8113 cells secreted soluble FLT-1 (sFLT-1) after infection with AdsFLT-1, and the conditioned medium from AdsFLT-1-treated Tca8113 cells seemed to inhibit VEGF-induced proliferation of human umbilical vein endothelial cells. The combined effects of sFLT-1 gene therapy and DDP chemotherapy was then studied in well-established Tca8113 xenografts. The concentration of sFLT-1 in serum reached a peak 8 days after intratumoral injection of AdsFLT-1. In these tumors, AdsFLT-1 intratumoral injections had only a small effect. Interestingly, when the cells were also exposed to DDP chemotherapy, significantly higher (P<0.05), and possibly synergistic, anti-tumoral effects were observed that were highly correlated to a marked reduction in intratumoral vascularization and an increase in tumor-cell apoptosis. Together, these data emphasize the potential of combining an anti-angiogenic gene therapy strategy with a destructive approach directed against the tumor cells to fight human tongue carcinoma.
Gao
Zhen-Nan
ZN
State Key Laboratory of Biotherapy, Sichuan University, Chengdu City 610041, PR China. zngao@sdu.edu.cn
Wei
Yu-Quan
YQ
Yang
Pi-Shan
PS
Xu
Xin
X
Zhao
Hua-Qiang
HQ
Huan
Xin
X
Kang
Bing
B
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002277:Carcinoma / Q000628:therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D014062:Tongue Neoplasms / Q000628:therapy*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D040281:Vascular Endothelial Growth Factor Receptor-1; D002945:Cisplatin