OBJECTIVE: To investigate the therapeutic effect of retroviral endostatin gene transfer on the human colon cancer cell line, LoVo. METHODS: A retroviral vector pLESSN expressing secretable endostatin was constructed and packaged with a titer of 8.2 x 10(5) CFU/ml. A LoVo cell line was subjected to retrovirus-mediated endostatin gene transfer. The proviral integration of endostatin was analyzed with PCR. The function of endostatin was tested by MTT assay in vitro and a mouse xenograft model in vivo. RESULTS: After transfection and superinfection, amphotropic retrovirus was collected, and transduction with amphotropic retroviruses resulted in endostatin proviral integration. The endostatin secreted by transduced LoVo cells markedly inhibited cell growth up to 67% (P<0.001), compared with the control cells. The gene expression of endostatin in LoVo colon tumor cells significantly inhibited tumor growth in vivo. There was an 86% reduction in tumor size in the endostatin-transduced group, accompanied by a reduction in vessels, compared with the control group (P<0.01). CONCLUSION: Retroviruses can allow functional expression of the endostatin gene in human colon tumors, showing promise for an antitumor strategy using antiangiogenesis.
OBJECTIVE: To investigate the therapeutic effect of retroviral endostatin gene transfer on the humancolon cancer cell line, LoVo. METHODS: A retroviral vector pLESSN expressing secretable endostatin was constructed and packaged with a titer of 8.2 x 10(5) CFU/ml. A LoVo cell line was subjected to retrovirus-mediated endostatin gene transfer. The proviral integration of endostatin was analyzed with PCR. The function of endostatin was tested by MTT assay in vitro and a mouse xenograft model in vivo. RESULTS: After transfection and superinfection, amphotropic retrovirus was collected, and transduction with amphotropic retroviruses resulted in endostatin proviral integration. The endostatin secreted by transduced LoVo cells markedly inhibited cell growth up to 67% (P<0.001), compared with the control cells. The gene expression of endostatin in LoVo colon tumor cells significantly inhibited tumor growth in vivo. There was an 86% reduction in tumor size in the endostatin-transduced group, accompanied by a reduction in vessels, compared with the control group (P<0.01). CONCLUSION: Retroviruses can allow functional expression of the endostatin gene in humancolon tumors, showing promise for an antitumor strategy using antiangiogenesis.
Authors: Torbjörn Åkerfeldt; Lena Gunningberg; Christine Leo Swenne; Göran Ronquist; Anders Larsson Journal: Eur J Med Res Date: 2014-11-08 Impact factor: 2.175