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长循环脂质体共包封姜黄素和阿霉素对 C26 小鼠结肠癌细胞的抗血管生成和抗炎作用。

Anti-angiogenic and anti-inflammatory effects of long-circulating liposomes co-encapsulating curcumin and doxorubicin on C26 murine colon cancer cells.

机构信息

Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, Cluj-Napoca, Romania; Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.

Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.

出版信息

Pharmacol Rep. 2018 Apr;70(2):331-339. doi: 10.1016/j.pharep.2017.10.004. Epub 2017 Oct 16.

Abstract

BACKGROUND

Emerging treatment options for colon cancer are needed to overcome the limitations regarding the side effects of current chemotherapeutics and drug resistance. The goal of this study was to assess the antitumor actions of PEGylated long-circulating liposomes (LCL) co-delivering curcumin (CURC) and doxorubicin (DOX) on murine colon carcinoma cells (C26).

METHODS

The cytotoxicity of CURC and DOX, administered alone or in combination, either in free or LCL form, was evaluated with regard to antiproliferative effects on C26 cells and to protumor processes that might be affected.

RESULTS

Our results indicated that PEGylated LCL-CURC-DOX exerted strong antiproliferative effects on C26 cells, slightly exceeding those induced by free CURC-DOX, but higher than either agent administered alone in their free form. These effects of LCL-CURC-DOX were due to the inhibition of the production of angiogenic/inflammatory proteins in a NF-κB-dependent manner, but were independent of ROS production or AP-1 c-Jun activation. Notable, the anti-angiogenic actions of LCL-CURC-DOX appeared to be much stronger than those induced by the co-administration of CURC and DOX in their free form, on C26 colon cancer cells.

CONCLUSION

LCL-CURC-DOX demonstrated enhanced cytotoxicity on C26 murine colon cancer cells by inhibiting the production of the majority of factors involved in tumor-associated angiogenesis and inflammation and is now being evaluated in vivo regarding its efficacy towards tumor growth in colon cancer.

摘要

背景

需要新兴的结肠癌治疗选择来克服当前化疗药物的副作用和耐药性的局限性。本研究的目的是评估载姜黄素(CURC)和阿霉素(DOX)的聚乙二醇化长循环脂质体(LCL)对小鼠结肠癌细胞(C26)的抗肿瘤作用。

方法

单独或联合使用游离或 LCL 形式的 CURC 和 DOX 的细胞毒性,就其对 C26 细胞的抗增殖作用以及可能受影响的促肿瘤过程进行了评估。

结果

我们的结果表明,PEGylated LCL-CURC-DOX 对 C26 细胞表现出强烈的抗增殖作用,略高于游离 CURC-DOX 诱导的作用,但高于游离形式单独给药的任何一种药物。LCL-CURC-DOX 的这些作用是由于 NF-κB 依赖性地抑制血管生成/炎症蛋白的产生,但与 ROS 产生或 AP-1 c-Jun 激活无关。值得注意的是,LCL-CURC-DOX 的抗血管生成作用似乎比游离形式的 CURC 和 DOX 联合给药在 C26 结肠癌细胞上诱导的作用要强得多。

结论

LCL-CURC-DOX 通过抑制与肿瘤相关的血管生成和炎症相关的大多数因子的产生,对 C26 小鼠结肠癌细胞表现出增强的细胞毒性,目前正在体内评估其对结肠癌肿瘤生长的疗效。

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