Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer
Significance of combination therapy of zoledronic acid and gemcitabine on pancreatic cancer
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DOI：
10.1111/j.1349-7006.2011.02113.x
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发表时间：
2012-01
期刊：
影响因子：
5.7
通讯作者：
Ming Zhao;Y. Tominaga;K. Ohuchida;K. Mizumoto;Lin Cui;S. Kozono;H. Fujita;Ryo Maeyama;H. Toma;Masao Tanaka
中科院分区：
文献类型：
--
作者：
Ming Zhao;Y. Tominaga;K. Ohuchida;K. Mizumoto;Lin Cui;S. Kozono;H. Fujita;Ryo Maeyama;H. Toma;Masao Tanaka
在本研究中，我们检测了唑来膦酸(ZOL)和吉西他滨(GEM)联合治疗在体内外对胰腺癌细胞的细胞毒作用。用ZOL、GEM或联合用药处理4株人胰腺癌细胞，观察不同用药方案对细胞增殖、侵袭及基质金属蛋白酶(MMPs)表达的影响。将胰腺癌细胞系移植于裸鼠脾内或原位，通过组织学和免疫组织化学方法评价这些药物对肿瘤转移和体内生长的影响。联合用药能有效抑制胰腺癌细胞的增殖(P<；0.001)和侵袭(P<；0.001)。Western blotting结果显示，ZOL治疗后，MMP2和MMP9的表达水平均降低。在体内，联合治疗显著抑制肿瘤生长(P<；0.05)和肝转移的发展(P<；0.05)。这些数据表明，ZOL和GEM联合使用时，对胰腺癌细胞具有显著的抗肿瘤、抗转移和抗血管生成作用。本研究首次利用体内模型报道了ZOL和GEM联合治疗胰腺癌的意义。这些数据为未来该药物方案在胰腺癌患者中的应用提供了良好的前景。(《癌症科学》2012；103：58-66)
In the present 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 cell 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 histological 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 ZOL and GEM, when used in combination, have significant antitumor, anti‐metastatic and anti‐angiogenic effects on pancreatic cancer cells. The present study is the first to report the significance of the combination treatment of ZOL and GEM in pancreatic cancer using an in vivo model. These data are promising for the future application of this drug regimen in patients with pancreatic cancer. (Cancer Sci 2012; 103: 58–66)