Cancer Management and Research (Jul 2019)
Paclitaxel-loaded nanobubble targeted to pro-gastrin-releasing peptide inhibits the growth of small cell lung cancer
Abstract
Jin-Ping Wang,1,2 Ji-Ping Yan,2 Jing Xu,1 Ting-Hui Yin,3 Rong-Qin Zheng,3 Wei Wang11Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, Shanxi 030006, People’s Republic of China; 2Department of Ultrasound, Shanxi Province People’s Hospital, Taiyuan, Shanxi 030012, People’s Republic of China; 3Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People’s Republic of ChinaObjective: 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.Keywords: paclitaxel, nanobubbles, proliferation, targeted therapy, small cell lung cancer