Abstract
Studies demonstrated that reduced PTEN levels are associated with poor prognoses of osteosarcoma. The nuclear localization of PTEN is important for its tumor suppressive function. Equally importantly, PTEN is the most significant negative regulator of PI3K/Akt signaling cascade, the constitutively activated pathway in osteosarcoma. In our study MG63 cells and U2OS cells were treated with the indicated concentrations of oxymatrine, in order to find the inhibition of oxymatrine to cells. We found the functions of oxymatrine on proliferation, apoptosis and invasion in cells. Oxymatrine could increase the expression of PTEN and promote its nuclear translocation in MG63 cells. In addition, oxymatrine could induce cell cycle arrest in G1 phase and apoptosis of MG63 cells. The migration and invasion potential of MG63 cells were also markedly inhibited by oxymatrine. Oxymatrine could suppress the growth and invasion of MG63 human osteosarcoma cells by up-regulating PTEN and promoting its nuclear translocation and inhibiting PI3K/Akt signaling pathway.
Highlights
Osteosarcoma (OS) is the most primary bone tumor and occurs predominantly in adolescents and young adults [1, 2]
Cells were treated with or without 20 μM OMT for 24h.The results showed that the increased degree of phosphate and tension homolog (PTEN) in cells treated with OMT was similar with that of cells silenced PTEN in both protein and mRNA levels (Figure1J, 1K), which indicated that OMT could promote endogenous PTEN expression
The nuclear import of PTEN is important in cell cycle regulation [10, 20].Studies reported that nuclear PTEN could facilitate G1 arrest and increase apoptosis in HEK293 cells [21, 22]
Summary
Osteosarcoma (OS) is the most primary bone tumor and occurs predominantly in adolescents and young adults [1, 2]. The genetic alterations of osteosarcoma include the inactivation of tumor suppressor genes and activation of oncogenes. As a tumor suppressor gene, pten was identified in 1997 which is altered in various types of solid tumors, mainly including osteosarcoma, melanoma, breast, prostate, endometrial cancer [6]. PTEN is one of the most commonly tumor suppressor in human cancers, which is a central negative regulator of thePI3K (phos-phoinositide-3 kinase)/ Akt signaling pathways for cell growth, metabolism, proliferation and survival [7, 8]. PTEN has very distinct roles in the cytoplasm and the nucleus. In the primary, differentiated, and resting cells, PTEN is predominantly localized cell nucleus, while cytoplasmic PTEN is predominately found in neoplastic tissues. PTEN displays a PI3K-independent manner and plays tumor suppressor role [8, 9]. The absence of nuclear PTEN is associated with more aggressive carcinoma and serves as a prognostic indicator [10]
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