Tetramethylpyrazine inhibits osteosarcoma cell proliferation via downregulation of NF-κB in vitro and in vivo

Wang,Yong; Fu,Qin; Zhao,Wei

doi:10.3892/mmr.2013.1611

Tetramethylpyrazine inhibits osteosarcoma cell proliferation via downregulation of NF-κB in vitro and in vivo

Authors:
- Yong Wang
- Qin Fu
- Wei Zhao
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Affiliations: Department of Orthopaedics, Shengjing Hospital, China Medical University, Shenyang, Liaoning 100004, P.R. China, Department of Orthopaedics, The Affiliated Central Hospital, Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China
Published online on: August 2, 2013 https://doi.org/10.3892/mmr.2013.1611
Pages: 984-988

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Abstract

Tetramethylpyrazine (TMP) is an effective component of the traditional Chinese medicine Chuanxiong, which has been reported to have beneficial effects in various types of cancer. However, the activity and mechanism of action of TMP in osteosarcoma (OS) have not been elucidated to date. The aim of the present study was to investigate the inhibitory effect of TMP on OS and its underlying mechanism of action. OS cells were treated with various concentrations of TMP for 48 h. BALB/c nude mice with OS were treated with an intraperitoneal injection of TMP at a dose of 100 mg/kg every other day for 28 days. Cell proliferation was evaluated using an MTT assay. Cell cycle and apoptosis were measured using flow cytometry. The protein expression of nuclear and cytosolic nuclear factor‑κB (NF-κB) p65, BCL‑2 and cyclin D1 was measured using western blot analysis. TMP inhibited the proliferation of OS cells (MG-63, SAOS-2 and U2OS) in a dose‑dependent manner. Additionally, TMP significantly induced apoptosis and G0/G1 arrest in MG-63 OS cells (P<0.05). TMP upregulated the protein expression of cytosolic NF-κB p65, while downregulating the protein expression of nuclear NF-κB p65, BCL-2 and cyclin D1. Furthermore, TMP exerted a significant antitumor effect against OS in a xenograft tumor mouse model and exhibited a low toxicity. The present study provided fundamental evidence for the application of TMP in chemotherapy against OS.

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