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1,25(OH)_2D_3和ATRA对HO8910生长的协同抑制作用

SYNERGISTIC INHIBITORY EFFECT OF 1,25(OH)_2D_3 AND ATRA ON GROWTH OF HUMAN OVARIANCANCER CELL LINE HO8910
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摘要 目的:通过单独或联合使用1,25-二羟维生素D3[1,25-dihydroxy vitaminD3,1,25(OH)2D3]和全反式维甲酸(all trans rinoic acid,ATRA),研究其对人卵巢癌细胞HO8910生长、细胞周期和细胞凋亡的影响,以及维生素D受体(vitamin D recept VDR)及维甲酸α受体受体(retinoic acid receptorα,RARα)mRNA的表达变化,探讨其作用的分子机制。方法:选用人卵巢癌细株HO8910在体外进行培养,培养时分别添加1,25(OH)2D3、ATRA或二者联合,采用MTT比色法测定细胞生长抑制率,流式细胞术(flow cytometry,FCM)进行细胞周期和细胞凋亡分析,用RT-PCR检测VDR及RARαmRNA的表达。结果:结果是单独或联合使用1,25-二羟维生素D3和全反式维甲酸诱导后,HO8910细胞生长均受到不同程度的抑制(P<0.05),并呈时间依赖关系;能够引起细胞周期时相的改变,G1细胞增多(P<0.05);能够诱导细胞产生细胞凋亡(P<0.05);能够上调VDR及RARαmRNA的表达(P<0.05),进而抑卵巢癌细胞增殖,其中以联合用药组最为显著。结论:说明1,25-二羟维生素D3和全反式维甲酸能抑制人卵巢癌细胞株HO8910生长;诱导细胞周期发生G1期阻滞,同时产生细胞凋亡作用;通过上调VDR及RARαmRNA的表达,从而抑制癌细胞增当1,25-二羟维生素D3与全反式维甲酸联合用药时,能够对HO8910细胞生长产生协同抑制作用。 Objective: To investigate the effects of 1,25-dihydroxy vitamin D3[1,25(OH)2D3] and all-trans retinoic acid(ATRA) on growth and cell cycle and apoptosis of human ovarian cancer cellsHO8910,and the expression of vitamin D receptor and the retinoic acid receptor α mRNA,then explore the molecular mechanism.Methods:HO8910 human ovarian cancer cell line were cultured in vitro and treaed with1,25(OH)2D3,ATRA,or the combination of both chemicals,cell proliferation was evaluated by MTT assay.Cell cycle and apoptosis were determined by flow cytometry(FCM).The expression of VDR and RAR α mRNA were determined by reverse transcription-polymerase chain reaction(RT-PCR).Results:The resulte showed that1,25(OH)2D3 and ATRA used alone or in combination,inhibited the growth of HO8910 cells in a time dependent manner(P〈0.05).FCM analysis indicated that1,25(OH)2D3 and ATRA used alone or in combination could change cell cycle of HO8910 cells(P〈0.05),increased the ratesofG1,induced apoptosis(P〈0.05).They could up-regulation of VDR and RAR α(P〈0.05),then inhibit proliferation of HO8910 cells.All of the effects were more obvious in the combination group than in 1,25(OH)2D3 or ATRA groups(P〈0.05).Conclusion:It is conclused that 1,25(OH)2D3 and ATRA could inhibit cell growth,change the cell cycle and induced G1 phase arrest of HO8910 cells,induce apoptosis,they could up-regulation of VDR or RAR α,then inhibit proliferation of HO8910 cells.Further more,the combination of1,25(OH)2D3 and ATRA could exert synergistic inhibitory efecton the growth of HO8910 cells.
出处 《内蒙古医学院学报》 2011年第1期29-33,共5页 Acta Academiae Medicinae Neimongol
关键词 1 25-二羟维生素D3[1 25(OH)2D3] 全反式维甲酸 细胞周期 细胞凋亡 1 25-dihydroxy vitaminD3[1 25(OH)2D3] all-trans retinoic acid(ATRA) cellcycle apoptosis
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