title: Endostatin gene therapy enhances the efficacy of paclitaxel to suppress breast cancers and metastases in mice.
abstract: Chemotherapy combined with antiangiogenic therapy is more effective than chemotherapy alone. The aim of this study was to investigate whether endostatin, a potent anti-angiogenic agent, could enhance the efficacy of paclitaxel to combat breast cancer. An expression plasmid encoding mouse endostatin (End-pcDNA3.1) was constructed, which produced intense expression of endostatin and inhibited angiogenesis in the chorioallantoic membrane assay. 4T1 breast tumors were established in BALB/c mice by subcutaneous injection of 1 x 10(5) 4T1 cells. The End-pcDNA3.1 plasmid diluted in the transfection reagent FuGENE was injected into the tumors (around 100 mm(2)), and paclitaxel was injected i.p. into the mice. Endostatin gene therapy synergized with paclitaxel in suppressing the growth of 4T1 tumors and their metastasis to the lung and liver. Both endostatin and paclitaxel inhibited tumor angiogenesis and induced cell apoptosis. Despite the finding that endostatin was superior to paclitaxel at inhibiting tumor angiogenesis, paclitaxel was nevertheless more effective at inducing tumor apoptosis. The combination of paclitaxel and endostatin was more effective in suppressing tumor growth, metastases, angiogenesis, and inducing apoptosis than the respective monotherapies. The combinational therapy with endostatin and paclitaxel warrants future investigation as a therapeutic strategy to combat breast cancer.
authors: Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Jinan, China.
authors: Jie
authors: J
authors: Li
authors: Xuesong
authors: X
authors: Dong
authors: Zongzhen
authors: Z
authors: Xu
authors: Xian
authors: X
authors: Jiang
authors: Hongchi
authors: H
authors: Jiang
authors: Geoffrey W
authors: GW
authors: Krissansen
authors: Xueying
authors: X
authors: Sun
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D019556:COS Cells; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D003131:Combined Modality Therapy; D043169:Endostatins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D017239:Paclitaxel / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043169:Endostatins; D011994:Recombinant Proteins; D017239:Paclitaxel