Endostatin gene therapy enhances the efficacy of paclitaxel to suppress breast cancers and metastases in mice |
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Authors: | Jie Li Xuesong Dong Zongzhen Xu Xian Jiang Hongchi Jiang Geoffrey W Krissansen Xueying Sun |
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Institution: | (1) Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Jinan, China;(2) The Hepatosplenic Surgery Center, Department of General Surgery, The First Clinical Medical School of Harbin Medical University, Harbin, China;(3) Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand |
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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 × 105 4T1 cells. The End-pcDNA3.1 plasmid diluted in the transfection reagent FuGENETM was injected into the tumors (around 100 mm2), 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. |
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Keywords: | endostatin paclitaxel breast cancer angiogenesis apoptosis |
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