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学位授与大学 |
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In this study, we examined the cytotoxic effects of combination therapy with zoledronic acid (ZOL) and gemcitabine (GEM) on pancreatic cancer cells in vitro and in vivo. Four human pancreatic cancer c...ell lines were treated with ZOL, GEM or a combination of both, and the effects of the respective drug regimens on cell proliferation, invasion and matrix metalloproteinase (MMP) expression were examined. A pancreatic cancer cell line was also intrasplenically or orthotopically implanted into athymic mice and the effects of these drugs on tumor metastasis and growth in vivo were evaluated by histologic and immunohistochemical analyses. Combination treatment with low doses of ZOL and GEM efficiently inhibited the proliferation (P < 0.001) and invasion (P < 0.001) of pancreatic cancer cells in vitro. Western blotting assay revealed that MMP-2 and MMP-9 expression levels were decreased after ZOL treatment. In vivo, combined treatment significantly inhibited tumor growth (P < 0.05) and the development of liver metastasis (P < 0.05). These data revealed that, when used in combination, ZOL and GEM have significant antitumor, anti-metastatic and anti-angiogenic effects on pancreatic cancer cells. In the present study, we first reported the significance of the combination treatment of ZOL and GEM in pancreatic cancer using an in vivo model. These data show promise for the future application of this drug regimen in patients with pancreatic cancer.続きを見る
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Abstract Introduction Materials and methods Results Discussion Acknowledgments Disclosure Statement References Figure legends
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