Antitumor activity of tetrandrine citrate in human glioma U87 cells in vitro and in vivo

Sun,Jingyu; Zhang,Yang; Zhen,Yongzhan; Cui,Ju; Hu,Gang; Lin,Yajun

doi:10.3892/or.2019.7372

Antitumor activity of tetrandrine citrate in human glioma U87 cells in vitro and in vivo

Authors:
- Jingyu Sun
- Yang Zhang
- Yongzhan Zhen
- Ju Cui
- Gang Hu
- Yajun Lin
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Affiliations: Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China, Peking University Fifth School of Clinical Medicine, Beijing 100730, P.R. China, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063000, P.R. China
Published online on: October 15, 2019 https://doi.org/10.3892/or.2019.7372
Pages: 2345-2354
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Since the current methods of treatment for malignant glioma, radiotherapy and chemotherapy, are unsatisfactory, the development of novel therapeutic compounds is required. In the present study, the inhibitory effect of tetrandrine citrate (TetC) on the proliferation of human glioma U87 cells, as well as its mechanism of action, were investigated. An MTT assay was used to assess cell viability in vitro, and the production of intracellular reactive oxygen species (ROS) was determined by assessing the fluorescence intensity of 2,7‑dichlorofluorescein (DCF). Flow cytometry was used to determine the level of apoptosis and cell cycle status, and the protein expression levels of apoptosis‑associated proteins were determined using western blotting. Additionally, the antitumor activity of TetC was assessed in vivo using a nude mouse xenograft model. The results revealed that in vitro, the proliferative rate of U87, U251 and human umbilical vein endothelial cells (HUVECs) was significantly reduced in a dose‑dependent manner following treatment with TetC, although TetC had the greatest inhibitory effect on U87 cells. The vacuolization and apoptosis of U87 cells was induced using 10 and 20 µmol/l TetC, respectively. The overall proliferative inhibition was associated with an increase in the levels of ROS and apoptosis. In TetC‑treated cells, the expression levels of apoptosis‑related proteins, including cleaved (CL) caspase‑3, Fas, phosphorylated (p)‑p38 and p‑JNK, were increased, whereas those of caspase‑3 and Bcl‑2 were decreased. In vivo, TetC was highly effective at inhibiting the growth of human glioma U87 xenografts in BALB/c nude mice, with a percentage growth inhibition of ≥68.7%. These findings indicated that the potent antitumor activity of TetC may be mediated through an increase in ROS levels, the downregulation of Bcl‑2, and the upregulation of CL caspase‑3, Fas, p‑p38 and p‑JNK expression levels.

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