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姜黄素-环糊精复合物增强吉西他滨在肺癌原位小鼠模型中的疗效。

Curcumin-cyclodextrin complexes potentiate gemcitabine effects in an orthotopic mouse model of lung cancer.

机构信息

Laboratory of Tumor and Development Biology, GIGA-Research (Groupe Interdisciplinaire de Génoprotéomique Appliquée) - GIGA-Cancer and GIGA-I, University of Liege and CHU of Liege, Sart-Tilman, 4000 Liege, Belgium.

出版信息

Br J Cancer. 2012 Sep 25;107(7):1083-92. doi: 10.1038/bjc.2012.379. Epub 2012 Aug 28.

Abstract

BACKGROUND

Overall clinical outcome for advanced lung cancer remains very disappointing despite recent advances in treatment. Curcumin has been reported as potentially active against cancer.

METHODS

Owing to poor curcumin solubility, we have used cyclodextrins (CD) as an excipient allowing a considerable increase of aqueous solubility and bioavailability of curcumin. The effects of solubilised curcumin have been evaluated in cell cultures as well as in an in vivo orthotopic lung tumour mouse model.

RESULTS

Cell proliferation was reduced while apoptosis rates were increased when lung epithelial tumour cells were cultured in the presence of curcumin-CD complexes. For in vivo experiments, cells were grafted into lungs of C57Bl/6 mice treated by an oral administration of a non-soluble form of curcumin, CDs alone or curcumin-CD complexes, combined or not with gemcitabine. The size of orthotopically implanted lung tumours was reduced upon curcumin complex administration as compared with treatments with placebo or non-solubilised curcumin. Moreover, curcumin potentiated the gemcitabine-mediated antitumour effects.

CONCLUSION

Our data demonstrate that curcumin, when given orally in a CD-solubilised form, reduces lung tumour size in vivo. In vitro experiments show impaired tumour cell proliferation and increased cell apoptosis. Moreover, our data underline a potential additive effect of curcumin with gemcitabine thus providing an efficient therapeutic option for antilung cancer therapy.

摘要

背景

尽管最近在治疗方面取得了进展,但晚期肺癌的整体临床疗效仍然非常令人失望。姜黄素已被报道具有潜在的抗癌活性。

方法

由于姜黄素的溶解度较差,我们使用环糊精(CD)作为赋形剂,使姜黄素的水溶解度和生物利用度有了相当大的提高。在细胞培养和体内原位肺肿瘤小鼠模型中评估了溶解的姜黄素的作用。

结果

当肺上皮肿瘤细胞在姜黄素-CD 复合物存在的情况下培养时,细胞增殖减少,而细胞凋亡率增加。对于体内实验,将细胞移植到 C57Bl/6 小鼠的肺部,并用口服给予非可溶性姜黄素、CD 单独或姜黄素-CD 复合物进行治疗,单独或联合使用吉西他滨。与安慰剂或未溶解的姜黄素治疗相比,姜黄素复合物给药后原位植入的肺肿瘤大小减小。此外,姜黄素增强了吉西他滨的抗肿瘤作用。

结论

我们的数据表明,以 CD 溶解形式口服给予姜黄素可减少体内肺肿瘤的大小。体外实验表明肿瘤细胞增殖受损,细胞凋亡增加。此外,我们的数据强调了姜黄素与吉西他滨的潜在协同作用,为肺癌的治疗提供了一种有效的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2847/3461170/a324acecad1c/bjc2012379f1.jpg

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