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负载蛇毒的二氧化硅纳米颗粒处理的人乳腺癌细胞对凋亡和生长停滞的易感性增加。

Increased susceptibility to apoptosis and growth arrest of human breast cancer cells treated by a snake venom-loaded silica nanoparticles.

作者信息

Badr Gamal, Sayed Douaa, Maximous Doaa, Mohamed Amany O, Gul Mustafa

机构信息

Laboratory of Immunology & Molecular Biology, Zoology Department, Faculty of Science, Assiut University, Assiut, Egypt.

出版信息

Cell Physiol Biochem. 2014;34(5):1640-51. doi: 10.1159/000366366. Epub 2014 Nov 3.

Abstract

BACKGROUND

The development of effective treatments against metastatic cancers, including breast cancer, is among the most important challenges in current experimental and clinical cancer research. We recently demonstrated that Walterinnesia aegyptia venom (WEV), either alone or in combination with silica nanoparticles (WEV+NP), resulted in the growth arrest and apoptosis of different cancer cell lines.

AIMS

In the present study, we evaluated the impact of WEV alone and WEV+NP on human breast cancer cells isolated from cancer biopsies.

METHODS

The potential effects of WEV alone and WEV+NP on the proliferation, induction of apoptosis and generation of free radicals in breast cancer cells isolated from 80 patients clinically diagnosed with breast cancer were evaluated by flow cytometry and ELISA.

RESULTS

WEV alone and WEV+NP inhibited the proliferation, altered the cell cycle and enhanced the induction of apoptosis of the breast cancer cells by increasing the activities of caspase-3, caspase-8 and caspase-9. In addition, the combination of WEV and NP robustly sensitized the breast cancer cells to growth arrest and apoptosis by increasing the generation of free radicals, including reactive oxygen species (ROS), hydroperoxide and nitric oxide. The combination of WEV with NP significantly enhanced the anti-tumor effect of WEV in breast cancer cells.

CONCLUSION

Our data indicate the therapeutic potential of the nanoparticle-sustained delivery of snake venom for the treatment of breast cancer.

摘要

背景

开发针对包括乳腺癌在内的转移性癌症的有效治疗方法,是当前癌症实验和临床研究中最重要的挑战之一。我们最近证明,埃及眼镜蛇毒(WEV)单独使用或与二氧化硅纳米颗粒联合使用(WEV+NP),可导致不同癌细胞系的生长停滞和凋亡。

目的

在本研究中,我们评估了单独使用WEV以及WEV+NP对从癌症活检中分离出的人乳腺癌细胞的影响。

方法

通过流式细胞术和酶联免疫吸附测定法,评估单独使用WEV以及WEV+NP对从80例临床诊断为乳腺癌的患者中分离出的乳腺癌细胞的增殖、凋亡诱导和自由基生成的潜在影响。

结果

单独使用WEV以及WEV+NP均可抑制乳腺癌细胞的增殖,改变细胞周期,并通过提高半胱天冬酶-3、半胱天冬酶-8和半胱天冬酶-9的活性来增强对乳腺癌细胞凋亡的诱导。此外,WEV与NP的组合通过增加包括活性氧(ROS)、过氧化氢和一氧化氮在内的自由基生成,使乳腺癌细胞对生长停滞和凋亡更敏感。WEV与NP的组合显著增强了WEV对乳腺癌细胞的抗肿瘤作用。

结论

我们的数据表明,纳米颗粒持续递送蛇毒在治疗乳腺癌方面具有治疗潜力。

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