β‑elemene enhances anticancer bone neoplasms efficacy of paclitaxel through regulation of GPR124 in bone neoplasms cells
- Zongze Wang
- Ying Li
- Fengxin Zhou
- Zhe Piao
- Jian Hao
Affiliations: Department of Orthopedics, Nankai Hospital of Tianjin, Tianjin 300100, P.R. China, Renal Department of Internal Medicine, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China
- Published online on: June 6, 2018 https://doi.org/10.3892/ol.2018.8909
Copyright: © Wang
et al. This is an open access article distributed under the
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The purpose of the present study was to investigate the anticancer effects of β‑elemene and paclitaxel for bone neoplasms. MTT assay, reverse transcription‑quantitative polymerase chain reaction, western blotting, flow cytometry and immunostaining were used to analyze the combined effects of β‑elemene and paclitaxel both in vitro and in vivo. The results demonstrated that combined treatment of β‑elemene and paclitaxel (β‑elemene‑paclitaxel) significantly inhibited growth and aggressiveness of U‑2OS cells compared with either β‑elemene or paclitaxel treatment alone. It was demonstrated that β‑elemene promoted paclitaxel‑induced apoptosis of U‑2OS cells. Anti‑apoptosis B‑cell lymphoma (Bcl)‑2 and Bcl‑w genes were downregulated and pro‑apoptotic Bcl‑2‑associated agonist of cell death and caspase‑3 genes were upregulated in U‑2OS cells following treatment with β‑elemene‑paclitaxel. Treatment of β‑elemene‑paclitaxel arrested the cell cycle and decreased cyclin‑dependent kinase, cyclin‑B1, P21 and P27 expression levels and decreased resistant genes alterations of ATP binding cassette subfamily B member 1, LDL receptor related protein and TS in U‑2OS cells. Results demonstrated that β‑elemene‑paclitaxel decreased G‑protein coupled receptor 124 (GPR124), vascular endothelial growth factor receptor, matrix metallopeptidase (MMP)‑3, MMP‑9 expression levels and increased endostatin, TIMP metallopeptidase inhibitor (TIMP)‑1, TIMP‑2 expression in U‑2OS cells. In vivo assay demonstrated that β‑elemene‑paclitaxel treatment inhibited tumor growth of BALB/c‑nu/nu nude mice and prolonged survival rate of tumor‑bearing mice. Immunostaining demonstrated that β‑elemene‑paclitaxel treatment increased apoptotic bodies, GPR124 and increased endostatin, TIMP‑1 and TIMP‑2 expression in tumor tissues. In conclusion, these results suggest that the combined treatment of β‑elemene‑paclitaxel is more effective at inhibiting bone neoplasm growth than β‑elemene or paclitaxel single treatment GPR124.