[Show abstract][Hide abstract] ABSTRACT: In our previous study, we detected decreased expression of phospho-Smad1/5/8 and its upstream signaling molecule, bone morphogenetic protein receptor IB subunit (BMPR-IB), in certain glioblastoma tissues, unlike normal brain tissues. In order to clarify the functional roles and mechanism of BMPR-IB in the development of glioblastoma, we studied the effects of BMPR-IB overexpression on glioblastoma cell lines in vitro and in vivo.
We selected glioblastoma cell lines U251, U87, SF763, which have different expression of BMPR-IB to be the research subjects. Colony formation analysis and FACS were used to detect the effects of BMPR-IB on the growth and proliferation of glioblastoma cells in vivo. Immunofluresence was used to detect the differentiation changes after BMPR-IB overexpression or knocking-down. Then we used subcutaneous and intracranial tumor models to study the effect of BMPR-IB on the growth and differentiation of glioblastoma cells in vivo. The genetic alterations involved in this process were examined by real-time PCR and western blot analysis.ed.
Forced BMPR-IB expression in malignant human glioma cells, which exhibit lower expression of BMPR-IB, induced the phosphorylation and nuclear localization of smad1/5/8 and arrested the cell cycle in G1. Additionally, BMPR-IB overexpression could suppress anchorage-independent growth and promote differentiation of theses glioblastoma cells. Furthermore, overexpression of BMPR-IB inhibited the growth of subcutaneous and intracranial tumor xenografts and prolonged the survival of mice injected intracranially with BMPR-IB-overexpressing glioblastoma cells. Conversely, inhibition of BMPR-IB caused SF763 malignant glioma cells, a line known to exhibit high BMPR-IB expression that does not form tumors when used for xenografts, to show increased growth and regain tumorigenicity in a nude mouse model system, ultimately shortening the survival of these mice. We also observed significant accumulation of p21 and p27kip1 proteins in response to BMPR-IB overexpression. Our study suggests that overexpression of BMPR-IB may arrest and induce the differentiation of glioblastoma cells due to upregulation of p21 and p27kip1 in vitro and that in vivo and decreased expression of BMPR-IB in human glioblastoma cells contributes to glioma tumorigenicity. BMPR-IB could represent a new potential therapeutic target for malignant human gliomas.
Journal of Experimental & Clinical Cancer Research 05/2012; 31(1):52. DOI:10.1186/1756-9966-31-52 · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: To investigate the effects of different magnetic simulations on cell proliferation, cell cycle, apoptosis, and cell differentiation of human fetal neural stem cell in vitro. Methods: Isolated neural stem cells were exposed to magnetic stimulation (with a frequency of 0.5 Hz, a wave wide of 72 μs and an intensity of 1.44 Tesla) once daily for 3 days. The cells were divided into three groups according to the pulses of magnetic stimulation each time: A group (thirty pulses each time), B group (sixty pulses each time), C group (ninety pulses each time) and D group (control group). MTT assay was applied to detect the proliferation activity of the neural stem cells, and flow cytometry was employed to detect the effect of magnetic stimulation on cell cycle, cell apoptosis, and cell differentiation. Results: The D values of neural stem cells in A, B, and C groups were significantly higher than those in the control group 24 to 48 hours after stimulation(P<0.05), indicating a slightly promoted proliferation of neural stem cells after magnetic stimulation. The proportions of G0/G1 phase cells of A, B, and C groups were less than those of the control group, and the proportion of G2/M-phase cells was higher than that of the control group. The proportions of β-tuberlin positive neurons in A, B, and C groups were higher than those in the control group as demonstrated by flow cytometry, and the proportion of neurons increased from 21.70% to 34.17% (P<0.05). Conclusion: Under proper condition, magnetic simulation can slightly promote cell proliferation and can induce neural stem cell differentiation into neurons in vitro, which may benefit neural function reconstruction.
Academic Journal of Second Military Medical University 04/2009; 29(4):373-377. DOI:10.3724/SP.J.1008.2009.00373