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靶向胃泌素释放肽前体的载紫杉醇纳米气泡抑制小细胞肺癌生长。

Paclitaxel-loaded nanobubble targeted to pro-gastrin-releasing peptide inhibits the growth of small cell lung cancer.

作者信息

Wang Jin-Ping, Yan Ji-Ping, Xu Jing, Yin Ting-Hui, Zheng Rong-Qin, Wang Wei

机构信息

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, Shanxi 030006, People's Republic of China.

Department of Ultrasound, Shanxi Province People's Hospital, Taiyuan, Shanxi 030012, People's Republic of China.

出版信息

Cancer Manag Res. 2019 Jul 16;11:6637-6649. doi: 10.2147/CMAR.S199175. eCollection 2019.

Abstract

OBJECTIVE

The aim of this work was to study the effects of paclitaxel-loaded nanobubbles targeting pro-gastrin-releasing peptide, designated as paclitaxel targeting nanobubbles, on small cell lung cancer (SCLC).

METHODS

Paclitaxel targeting nanobubbles were prepared by Thin-film hydration method. Subsequently, the prepared nanomaterials were tested for their in vitro effects on SCLC H446 cells proliferation, apoptosis and motility using the CCK-8 assay, flow cytometry and cell scratch test. Next, the potential molecular regulatory mechanisms of the prepared nanomaterials on H446 cells were evaluated by RT-PCR, Western blot and immunohistochemical detection. Finally, the in vivo effects of the constructed nanomaterials were assessed on SCLC tumor using tumor-burdened nude mice models.

RESULTS

Paclitaxel targeting nanobubbles significantly inhibited SCLC cell proliferation and migration, and promoted cell apoptosis. Moreover, the expression levels of Bcl-2, survivin, CDK2 and MMP-2 significantly decreased in SCLC cells treated with paclitaxel targeting nanobubbles, whereas the expression of caspase-3 and Rb were increased. There was a notable decrease in tumor size in vivo in SCLC nude mice models treated with paclitaxel targeting nanobubbles.

CONCLUSION

Paclitaxel targeting nanobubbles effectively inhibited the proliferation, migration and invasion of SCLC cells and induced SCLC cells apoptosis. Hence, these nanobubbles show potential in SCLC-targeted drug treatment application.

摘要

目的

本研究旨在探讨靶向胃泌素释放肽的紫杉醇纳米气泡(称为紫杉醇靶向纳米气泡)对小细胞肺癌(SCLC)的影响。

方法

采用薄膜水化法制备紫杉醇靶向纳米气泡。随后,使用CCK-8法、流式细胞术和细胞划痕试验检测所制备的纳米材料对SCLC H446细胞增殖、凋亡和迁移的体外作用。接下来,通过RT-PCR、Western印迹和免疫组化检测评估所制备的纳米材料对H446细胞的潜在分子调控机制。最后,使用荷瘤裸鼠模型评估所构建的纳米材料对SCLC肿瘤的体内作用。

结果

紫杉醇靶向纳米气泡显著抑制SCLC细胞增殖和迁移,并促进细胞凋亡。此外,用紫杉醇靶向纳米气泡处理的SCLC细胞中,Bcl-2、survivin、CDK2和MMP-2的表达水平显著降低,而caspase-3和Rb的表达增加。用紫杉醇靶向纳米气泡处理的SCLC裸鼠模型体内肿瘤大小显著减小。

结论

紫杉醇靶向纳米气泡有效抑制SCLC细胞的增殖、迁移和侵袭,并诱导SCLC细胞凋亡。因此,这些纳米气泡在SCLC靶向药物治疗应用中显示出潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e28b/6642650/44d96bdf556a/CMAR-11-6637-g0001.jpg

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