AIM: To study the antitumor effect of combined gene therapy of endostatin and interleukin 12 (IL-12) with polyvinylpyrrolidone (PVP) on mouse transplanted hepatoma.METHODS: Mouse endostatin eukaryotic plasmid (pSecES)...AIM: To study the antitumor effect of combined gene therapy of endostatin and interleukin 12 (IL-12) with polyvinylpyrrolidone (PVP) on mouse transplanted hepatoma.METHODS: Mouse endostatin eukaryotic plasmid (pSecES) with a mouse Igk signal sequence inside and mouse IL-12 eukaryotic plasmid (pmIL-22) were transfected into BHK-22cells respectively. Endostatin and IL-22 were assayed by ELISA from the supernant and used to culture endothelial cells and spleen lymphocytes individually. Proliferation of the latter was evaluated by M-I-r. H22 cells were inoculated into the leg musde of mouse, which was injected intratumorallywith pSecES/PVP, pmIL-12/PVP or pSecES+pmIL-12/PVPrepeatedly. Tumor weight, serum endostatin and serumIL-22 were assayed. Tumor infiltrating lymphocytes, tumormicrovessel density and apoptosis of tumor cells were also displayed by HE staining, CD32 staining and TUNEL.RESULTS: Endostatin and IL-12 were secreted after transfection, which could inhibit the proliferation of endothelial cells or promote the proliferation of spleen lymphocytes.Tumor growth was highly inhibited by 92.8% after injection of pSecES+pmIL-i2/PVP accompanied by higher serum endostatin and IL-22, more infiltrating lymphocytes, fewertumor vessels and more apoptosis cells compared with injection of pSecES/PVP, pmIL-i2/PVP or vector/PVP.CONCLUSION: Mouse endostatin gene and IL-12 gene can be expressed after intratumoral injection with PVP.Angiogenesis of hepatoma can be inhibited synergisticly,lymphocytes can be activated to infiltrate, and tumor cells are induced to apoptosis. Hepatoma can be highly inhibited or eradiated.展开更多
基金Supported by the Major State Basic Research Development Program of China 973 Program,No.2002CB513100
文摘AIM: To study the antitumor effect of combined gene therapy of endostatin and interleukin 12 (IL-12) with polyvinylpyrrolidone (PVP) on mouse transplanted hepatoma.METHODS: Mouse endostatin eukaryotic plasmid (pSecES) with a mouse Igk signal sequence inside and mouse IL-12 eukaryotic plasmid (pmIL-22) were transfected into BHK-22cells respectively. Endostatin and IL-22 were assayed by ELISA from the supernant and used to culture endothelial cells and spleen lymphocytes individually. Proliferation of the latter was evaluated by M-I-r. H22 cells were inoculated into the leg musde of mouse, which was injected intratumorallywith pSecES/PVP, pmIL-12/PVP or pSecES+pmIL-12/PVPrepeatedly. Tumor weight, serum endostatin and serumIL-22 were assayed. Tumor infiltrating lymphocytes, tumormicrovessel density and apoptosis of tumor cells were also displayed by HE staining, CD32 staining and TUNEL.RESULTS: Endostatin and IL-12 were secreted after transfection, which could inhibit the proliferation of endothelial cells or promote the proliferation of spleen lymphocytes.Tumor growth was highly inhibited by 92.8% after injection of pSecES+pmIL-i2/PVP accompanied by higher serum endostatin and IL-22, more infiltrating lymphocytes, fewertumor vessels and more apoptosis cells compared with injection of pSecES/PVP, pmIL-i2/PVP or vector/PVP.CONCLUSION: Mouse endostatin gene and IL-12 gene can be expressed after intratumoral injection with PVP.Angiogenesis of hepatoma can be inhibited synergisticly,lymphocytes can be activated to infiltrate, and tumor cells are induced to apoptosis. Hepatoma can be highly inhibited or eradiated.
