联合诺斯卡品通过抗血管生成和凋亡途径增强吉西他滨对非小细胞肺癌的抗癌活性。

Enhanced anticancer activity of gemcitabine in combination with noscapine via antiangiogenic and apoptotic pathway against non-small cell lung cancer.

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, University of Hawaii, Hilo, Hawaii, United States of America.

出版信息

PLoS One. 2011;6(11):e27394. doi: 10.1371/journal.pone.0027394. Epub 2011 Nov 15.

BACKGROUND

The aim of this investigation was to evaluate the anticancer activity of Noscapine (Nos) and Gemcitabine (Gem) combination (NGC) against non-small cell lung cancer (NSCLC) and to elucidate the underlying mechanism of action.

METHODS

Isobolographic method was used to calculate combination index values from cytotoxicity data. In vitro antiangiogenic and apoptotic activity of Nos, Gem and NGC was evaluated. For in vivo studies, female athymic Nu/nu mice were xenografted with H460 tumors and the efficacy of Nos, Gem, or NGC was determined. Protein expressions by immunohistochemical staining were evaluated in harvested tumor tissues.

RESULTS

The CI values (<0.59) were suggestive of synergistic behavior between Nos and Gem. NGC treatment showed significantly inhibited tube formation and increased percentage of apoptotic cells. NGC, Gem and Nos treatment reduced tumor volume by 82.9±4.5 percent, 39.4±5.8 percent and 34.2±5.7 percent respectively. Specifically, NGC treatment decreased expression cell survival proteins; VEGF, CD31 staining and microvessel density and enhanced DNA fragmentation and cleaved caspase 3 levels compared to single agent treated and control groups.

CONCLUSION

Nos potentiated the anticancer activity of Gem in an additive to synergistic manner against lung cancer via antiangiogenic and apoptotic pathways. These findings suggest potential benefit for use of NGC chemotherapy for treatment of lung cancer.

背景

本研究旨在评估纳库布宁（Nos）和吉西他滨（Gem）联合（NGC）对非小细胞肺癌（NSCLC）的抗癌活性，并阐明其作用机制。

方法

采用等辐射法从细胞毒性数据中计算组合指数值。评估 Nos、Gem 和 NGC 的体外抗血管生成和促凋亡活性。在体内研究中，雌性无胸腺 Nu/nu 小鼠异种移植 H460 肿瘤，测定 Nos、Gem 或 NGC 的疗效。通过免疫组织化学染色评估收获的肿瘤组织中的蛋白表达。

结果

CI 值（<0.59）提示 Nos 和 Gem 之间存在协同作用。NGC 治疗可显著抑制管腔形成并增加凋亡细胞的百分比。与单独用药组和对照组相比，NGC、Gem 和 Nos 治疗使肿瘤体积分别减少 82.9±4.5%、39.4±5.8%和 34.2±5.7%。具体而言，与单独用药组和对照组相比，NGC 治疗降低了细胞存活蛋白（VEGF、CD31 染色和微血管密度）的表达，同时增强了 DNA 片段化和 cleaved caspase 3 水平。