Fangchinoline suppresses the proliferation, invasion and tumorigenesis of human osteosarcoma cells through the inhibition of PI3K and downstream signaling pathways

Li,Xiucheng; Yang,Zhifan; Han,Weiqi; Lu,Xuanyuan; Jin,Songtao; Yang,Wanlei; Li,Jianlei; He,Wei; Qian,Yu

doi:10.3892/ijmm.2017.3013

Fangchinoline suppresses the proliferation, invasion and tumorigenesis of human osteosarcoma cells through the inhibition of PI3K and downstream signaling pathways

Authors:
- Xiucheng Li
- Zhifan Yang
- Weiqi Han
- Xuanyuan Lu
- Songtao Jin
- Wanlei Yang
- Jianlei Li
- Wei He
- Yu Qian
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Affiliations: Department of Orthopaedics, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China
Published online on: June 6, 2017 https://doi.org/10.3892/ijmm.2017.3013
Pages: 311-318
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma is the most common malignant bone tumor. Most patients diagnosed with osteosarcoma are less than 20 years of age. Osteosarcoma cells proliferate rapidly and invade other tissues. At present, neoadjuvant chemotherapy is the primary pharmacodynamic strategy to prevent the progression of osteosarcoma. However, adverse effects of this strategy limit its long‑term application. Previous research has shown that fangchinoline exerts antitumor effects on several types of tumor cells; however, its effect on osteosarcoma cells remains unknown. The present study evaluated the effects of fangchinoline on the proliferation, apoptosis, migration and invasion of osteosarcoma cells in vitro and on their tumorigenesis in vivo and determined the possible underlying mechanism of action. Fangchinoline‑treated MG63 and U20S cells showed significantly decreased proliferation and significantly increased apoptosis. Fangchinoline markedly suppressed the migration and invasion of the MG63 cells. Fangchinoline‑treated MG63 cells showed significantly decreased expression of phosphoinositide 3‑kinase (PI3K) and Aktp‑Thr308. Moreover, fangchinoline‑treated MG63 cells showed downregulated expression of cyclin D1 and matrix metalloproteinase 2 and 9, which act downstream of PI3K, and upregulated expression of caspase‑3 and caspase‑8. Furthermore, fangchinoline suppressed the growth of subcutaneous osteosarcoma tumors in Balb/c mice subcutaneously injected with osteosarcoma cells. These findings suggest that fangchinoline inhibits the progression of osteosarcoma by suppressing the proliferation, migration and invasion and by accelerating the apoptosis of osteosarcoma cells. In addition, our results suggest that the mechanism underlying the antitumor effects of fangchinoline involve the inhibition of PI3K and its downstream signaling pathways.

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