Oncotarget

Research Papers:

Application of luteolin nanomicelles anti-glioma effect with improvement in vitro and in vivo

Songping Zheng, Yongzhong Cheng, Yan Teng, Xiaoxiao Liu, Ting Yu, Yi Wang, Jiagang Liu, Yuzhu Hu, Cong Wu, Xiang Wang, Yanhui Liu, Chao You, Xiang Gao _ and Yuquan Wei

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Oncotarget. 2017; 8:61146-61162. https://doi.org/10.18632/oncotarget.18019

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Abstract

Songping Zheng1,*, Yongzhong Cheng1,*, Yan Teng1, Xiaoxiao Liu1, Ting Yu1, Yi Wang1, Jiagang Liu1, Yuzhu Hu1, Cong Wu1, Xiang Wang1, Yanhui Liu1, Chao You1, Xiang Gao1 and Yuquan Wei1

1Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China

*These authors have contributed equally to this work

Correspondence to:

Xiang Gao, email: xiangxianggao2008@163.com

Keywords: luteolin, glioma, chemotherapy, nanoparticles

Received: February 20, 2017     Accepted: April 11, 2017     Published: May 19, 2017

ABSTRACT

Glioblastoma multiforme (GBM) is one of the most common and malignant tumor. Luteolin, a polyphenolic compound, has been proposed to have anti-tumor activity against various cancers. However, the greatest obstacle in the administration of luteolin is its hydrophobicity as well as the low oral bioavailability. In this study, we formulated luteolin-loaded MPEG-PCL (Luteolin/MPEG-PCL) micelles aiming to improve its solubility in aqueous solution and investigate the anti-tumor effect on glioma in vitro and in vivo. The spherical Luteolin/MPEG-PCL micelles were completely dispersible in normal saline and could release luteolin in a sustained manner in vitro. We demonstrated that Luteolin/MPEG-PCL micelles had stronger cytotoxicity and induced a higher percentage of apoptosis in C6 and U87 cells than free luteolin in vitro. The immunohistochemical study revealed that Luteolin/MPEG-PCL micelles induced more glioma cell apoptosis than free luteolin and inhibited neovascularization in tumor tissues. The Pro-caspase9 and Bcl-2 down-regulation and cleaved-caspase9 and Bax up-regulation suggested that luteolin induced apoptosis via the mitochondrial pathway in vitro. What is more, we found the drug could cumulated much more in the nano-drug group than free drug group through imaging in vivo. In conclusion, the Luteolin/MPEG-PCL micelles have the potential clinical application in glioma chemotherapy.


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