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氧-碳纳米管作为紫杉醇治疗乳腺癌的化疗增敏剂

Oxygen-carbon nanotubes as a chemotherapy sensitizer for paclitaxel in breast cancer treatment.

作者信息

Wang Yongkun, Wang Chuanying, Jia Yijun, Cheng Xianhua, Lin Qing, Zhu Mingjie, Lu Yunshu, Ding Longlong, Weng Ziyi, Wu Kejin

机构信息

Department of General Surgery, XinHua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

School of Mechanical and Power Engineering, Shanghai Jiaotong University, Shanghai, China.

出版信息

PLoS One. 2014 Aug 4;9(8):e104209. doi: 10.1371/journal.pone.0104209. eCollection 2014.

Abstract

OBJECTIVE

To study the in vivo and in vitro effects of adding oxygen carbon nanotubes (CNTs) to chemotherapy for breast cancer.

METHODS

MCF-7 and SK-BR-3 breast cancer cells were co-cultured with paclitaxel and then exposed to oxygen-CNTs under hypoxic conditions. Cell proliferation, viability, and apoptosis rate were analyzed. Hypoxia-inducible factor-1 alpha (HIF-1α) expression was measured using reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Nude mice were used as a human breast cancer model to explore the impact of oxygen-CNTs on the in vivo chemotherapeutic effect of paclitaxel.

RESULTS

Oxygen-CNTs had no significant effects on the growth of breast cancer cells under normoxia and hypoxia. However, in the hypoxic environment, oxygen-CNTs significantly enhanced the inhibitory effect of paclitaxel on cell proliferation, as well as the apoptosis rate. Under hypoxia, downregulation of HIF-1α and upregulation of caspase-3, caspase-8, caspase-9, LC3 and Beclin-1 were observed when paclitaxel was combined with oxygen-CNT. Furthermore, addition of oxygen-CNTs to chemotherapy was found to significantly reduce tumor weight in the tumor-bearing mice model.

CONCLUSIONS

Oxygen-CNTs can significantly increase the chemotherapeutic effect of paclitaxel on breast cancer cells. Oxygen-CNTs may be a potential chemosensitizer in breast cancer therapy.

摘要

目的

研究添加氧碳纳米管(CNTs)至乳腺癌化疗中的体内和体外效果。

方法

将MCF-7和SK-BR-3乳腺癌细胞与紫杉醇共培养,然后在缺氧条件下暴露于氧碳纳米管。分析细胞增殖、活力和凋亡率。使用逆转录-聚合酶链反应(RT-PCR)和蛋白质印迹法测量缺氧诱导因子-1α(HIF-1α)的表达。使用裸鼠作为人乳腺癌模型,探讨氧碳纳米管对紫杉醇体内化疗效果的影响。

结果

在常氧和缺氧条件下,氧碳纳米管对乳腺癌细胞的生长无显著影响。然而,在缺氧环境中,氧碳纳米管显著增强了紫杉醇对细胞增殖的抑制作用以及凋亡率。在缺氧条件下,当紫杉醇与氧碳纳米管联合使用时,观察到HIF-1α下调以及caspase-3、caspase-8、caspase-9、LC3和Beclin-1上调。此外,发现在荷瘤小鼠模型中,化疗添加氧碳纳米管可显著减轻肿瘤重量。

结论

氧碳纳米管可显著提高紫杉醇对乳腺癌细胞的化疗效果。氧碳纳米管可能是乳腺癌治疗中的一种潜在化学增敏剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f634/4121325/91f66d7986ad/pone.0104209.g001.jpg

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