Background RNA interference （RNAi） technology is emerging as a very potent tool to generate a cellular knockdown of a desired gene. The aim of this study was to explore whether RNAi targeting vascular endothelial gr...Background RNA interference （RNAi） technology is emerging as a very potent tool to generate a cellular knockdown of a desired gene. The aim of this study was to explore whether RNAi targeting vascular endothelial growth factor-C （VEGF-C） could inhibit colorectal tumor lymphangiogenesis and tumor growth. Methods We used vector-based RNAi to inhibit VEGF-C expression in colon cancer in vitro and in vivo. VEGF-C expression was quantified by real-time polymerase chain reaction and Westen blotting. To establish LoVo cell tumor xenografts in mice, we subcutaneously inoculated 1.0×10^6 LoVo cells in nude mice; after injection, tumors were allowed to grow for 4 weeks until the volume reached （75.80± 55.8）mm^3. The mice were then randomly divided into two groups： （1） the VEGF-C-siRNA group （n= 10） received direct injection of ＂therapeutic＂ plasmid 50 IJg of LoVo-VEGF-C-siRNA into the tumor mass; （2） the control group （n= 10） were injected with LoVo-control in 20 IJI of sterile 0.9% NaCI solution into the tumor mass. Tumor growth, microlymphatics and microvessels were compared for mice administered either systemic VEGF-C-siRNA or control over 4 weeks. Results The mRNA and protein expression of VEGF-C in the colon tumor cell line, LoVo, stably transfected with a VEGF-C-siRNA vector, were significantly downregulated 45.3% and 35.3% respectively. In vivo, four weeks after injection, the tumor volume were significantly smaller in VEGF-C-siRNA group than in LoVo-control group （（314.8 ± 54.8） mm3 vs （553.9 ± 90.1） mm3）; the incidences of lymph node metastasis （30%） in VEGF-C-siRNA were significantly inhibited compared with LoVo-control group （70%）; in VEGF-C-siRNA group, the number of microlymphatics per microscopic field was （5.3 ± 0.7） and the number of microvessels per microscopic field was （24.2 ± 6.5） decreased compared with LoVo-control group （12.5 ± 6.9） and （42.1 ± 7.4） （all P〈0.001）. Conclusion Inhibition of VEGF-C expression using siRNA展开更多
The relationship between vascular endothelial growth factor-C （VEGF-C）/vascular endothelial growth factor receptor 3 （VEGFR-3） expression and clinicopathologic features of the patients with non-small cell lung can...The relationship between vascular endothelial growth factor-C （VEGF-C）/vascular endothelial growth factor receptor 3 （VEGFR-3） expression and clinicopathologic features of the patients with non-small cell lung cancer （NSCLC） was investigated. The expression of VEGF-C and VEGFR-3 was assessed in 65 patients with NSCLC by immunohistochemistry. The significance of VEGF-C and VEGFR-3 expression was analyzed statistically. The results showed that VEGF-C and VEGFR-3 were highly expressed in cytoplasm and membrane in lung cancer tissues with the positive rate being 55.4 % and 52.3 % respectively, while there was no expression in the normal lung tissues. The expression of VEGF-C was significantly increased in adenocacinoma as compared to other types of NSCLC （P〈0.05）. The VEGFR-3 expression was closely related with lymph node metastasis （P〈0.01） and TNM stage （P〈0.05）. There was a positive correlation between the VEGF-C and VEGFR-3 expression in NSCLC patients （r=-0.658, P〈0.01）. It is suggested that VEGFR-3 plays an important role in the lymphatic metastasis of NSCLC. The interaction between VEGF-C and VEGFR-3 may be deeply involved in the mechanism of lung cancer metastasis.展开更多
文摘Background RNA interference （RNAi） technology is emerging as a very potent tool to generate a cellular knockdown of a desired gene. The aim of this study was to explore whether RNAi targeting vascular endothelial growth factor-C （VEGF-C） could inhibit colorectal tumor lymphangiogenesis and tumor growth. Methods We used vector-based RNAi to inhibit VEGF-C expression in colon cancer in vitro and in vivo. VEGF-C expression was quantified by real-time polymerase chain reaction and Westen blotting. To establish LoVo cell tumor xenografts in mice, we subcutaneously inoculated 1.0×10^6 LoVo cells in nude mice; after injection, tumors were allowed to grow for 4 weeks until the volume reached （75.80± 55.8）mm^3. The mice were then randomly divided into two groups： （1） the VEGF-C-siRNA group （n= 10） received direct injection of ＂therapeutic＂ plasmid 50 IJg of LoVo-VEGF-C-siRNA into the tumor mass; （2） the control group （n= 10） were injected with LoVo-control in 20 IJI of sterile 0.9% NaCI solution into the tumor mass. Tumor growth, microlymphatics and microvessels were compared for mice administered either systemic VEGF-C-siRNA or control over 4 weeks. Results The mRNA and protein expression of VEGF-C in the colon tumor cell line, LoVo, stably transfected with a VEGF-C-siRNA vector, were significantly downregulated 45.3% and 35.3% respectively. In vivo, four weeks after injection, the tumor volume were significantly smaller in VEGF-C-siRNA group than in LoVo-control group （（314.8 ± 54.8） mm3 vs （553.9 ± 90.1） mm3）; the incidences of lymph node metastasis （30%） in VEGF-C-siRNA were significantly inhibited compared with LoVo-control group （70%）; in VEGF-C-siRNA group, the number of microlymphatics per microscopic field was （5.3 ± 0.7） and the number of microvessels per microscopic field was （24.2 ± 6.5） decreased compared with LoVo-control group （12.5 ± 6.9） and （42.1 ± 7.4） （all P〈0.001）. Conclusion Inhibition of VEGF-C expression using siRNA
文摘The relationship between vascular endothelial growth factor-C （VEGF-C）/vascular endothelial growth factor receptor 3 （VEGFR-3） expression and clinicopathologic features of the patients with non-small cell lung cancer （NSCLC） was investigated. The expression of VEGF-C and VEGFR-3 was assessed in 65 patients with NSCLC by immunohistochemistry. The significance of VEGF-C and VEGFR-3 expression was analyzed statistically. The results showed that VEGF-C and VEGFR-3 were highly expressed in cytoplasm and membrane in lung cancer tissues with the positive rate being 55.4 % and 52.3 % respectively, while there was no expression in the normal lung tissues. The expression of VEGF-C was significantly increased in adenocacinoma as compared to other types of NSCLC （P〈0.05）. The VEGFR-3 expression was closely related with lymph node metastasis （P〈0.01） and TNM stage （P〈0.05）. There was a positive correlation between the VEGF-C and VEGFR-3 expression in NSCLC patients （r=-0.658, P〈0.01）. It is suggested that VEGFR-3 plays an important role in the lymphatic metastasis of NSCLC. The interaction between VEGF-C and VEGFR-3 may be deeply involved in the mechanism of lung cancer metastasis.
