期刊文献+

人骨形态发生蛋白12对人骨肉瘤细胞的生物学作用 被引量:2

Effects of Human Bone Morphogenetic Protein-12 on Osteosarcoma Cell Line MG63 and U2OS
在线阅读 下载PDF
导出
摘要 为研究人骨形态发生蛋白(human bone morphogenetic proteins,hBMP)12对人骨肉瘤细胞株MG63和U2OS的作用,分别用hBMP12重组腺病毒(AdBMP12)以及含重组hBMP12(recombinant hBMP12,rhBMP12)的条件培养液干预人骨肉瘤细胞MG63和U2OS,利用台盼蓝拒染法、TUNEL法、吖啶橙/溴乙啶(AO/EB)荧光双染法、Transwell小室和碱性磷酸酶活性测定法分别检测细胞增殖、凋亡、迁移以及成骨分化能力的变化.与相应对照组相比,AdBMP12和含rhBMP12的条件培养液的干预致两种骨肉瘤细胞株细胞存活率降低,并呈一定的时间依赖性;凋亡率均随时间延长而增加,并且两种检测方法的结果一致;不同时间点的细胞穿膜数均明显减低;碱性磷酸酶活性在干预3d后开始逐渐增加,至第9d仍可观测到.以上差异均有统计学意义(P<0.01).提示无论是以腺病毒介导基因转入还是重组蛋白直接作用方式,hBMP12都可以抑制人骨肉瘤细胞株MG63和U2OS的增殖和迁移,并诱导其凋亡和向成骨细胞分化. In order to investigate the effects of hBMP12 on osteosarcoma cell MG63 and U2OS, Adenovirus-BMP12 (Ad-BMP12) and recombinant human BMP12-conditioned media (rhBMP12-CM) were used to treat the cell lines. Their proliferation, apoptosis, and transmigration were detected by Trypan blue exclusion test, TdT-mediated biotinylated-dUTP nick end labling (TUNEL), acridine orange-ethidium bromide (AO/EB) double fluorescent dye staining, and transwell-room test, respectively. The alkaline phosphatase (ALP) activity was detected to reflect the differentiation of tumors. Compared with the control groups, the cell survival rates of experimental groups which treated with AdBMP12 or rhBMP12-CM showed a significant time-dependent decrease (P〈 0.01 ). The apoptosis indexes were increased significantly (P〈 0.01 ) and the results from TUNEL and AO/EB method were consistent. The cell numbers of transmembrane significantly decreased at three detecting time points for the two cell lines (P〈 0.01 ). BMP12 treatment enhanced the activity of ALP of both cell lines within 3 days and this effect was observed at least up to day 9 of the treatment (P〈0.01). In conclusion, hBMP12 could inhibit the proliferation and transmigration of osteosarcoma cells, induce their apoptosis and differentiate into osteoblasts in osteosarcoma cell lines MG63 and U2OS.
出处 《生命科学研究》 CAS CSCD 2008年第4期365-372,共8页 Life Science Research
基金 重庆市自然科学基金资助项目(CSCT2005BB5320)
关键词 骨形态发生蛋白 细胞增殖 细胞凋亡 细胞迁移 碱性磷酸酶活性 bone morphogenetic protein proliferation transmigration apoptosis the activity of alkaline phosphatase
  • 相关文献

参考文献11

  • 1BLEUMING S A, HE X C, KODACH L L, et al. Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice[J]. Cancer Res, 2007,67(17):8149-8155.
  • 2LAI T H, FONG Y C, FU W M, et al. Osteoblasts-derived BMP-2 enhances the motility of prostate cancer cells via activation of integrins[J]. Prostate, 2008 ,68(12) : 1341-1353.
  • 3HJERTNER O, HJORTH-HANSEN H, BORSET M, et al. Bone morphogenetic protein-4 inhibits proliferation and induces apoptosis of multiple myeloma cells[J]. Blood, 2001,97(2):516-522.
  • 4LUO J, DENG Z L, LUO X, et al. A protocol for rapid generation of recombinant adenoviruses using the AdEasy system[J]. Nature Protocols, 2007,2 ( 5 ) : 1236-1247.
  • 5左国伟,何焕玲,李星星,赖天霞,王嫣,王胜,周兰.腺病毒介导BMP-2和BMP-6对人骨肉瘤细胞株MG63和U2OS的作用研究[J].第三军医大学学报,2007,29(18):1768-1771. 被引量:8
  • 6吴兴,陈峥嵘,张光健.AO/EB双重染色法检测人骨肉瘤细胞凋亡[J].肿瘤,2004,24(1):88-89. 被引量:15
  • 7何焕玲,李星星,赖天霞,左国伟,谭启华,周兰.BMP-2、-3、-6和-12在骨肉瘤细胞株中的表达[J].中国组织化学与细胞化学杂志,2007,16(2):134-137. 被引量:9
  • 8LAWTON L N, BONALDO M F, JELENC P C. Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta[J]. Gene, 1997,203( 1 ) : 17-26.
  • 9FURUYA K, NIFUJI A, ROSEN V, et al. Effects of GDF7/ BMP12 on proliferation and alkaline phosphatase expression in rat osteoblastic osteosarcoma ROS 17/2.8 cells[J]. Cell Biochem, 1999,72(2): 177-180.
  • 10INADA M, KATAGIRI T, AKIYAMA S, et al. Bone morphogenetic protein-12 and -13 inhibit terminal differentiation of myoblasts, but do not induce their differentiation into osteoblasts[J]. Biochem Biophys Res Commun, 1996,222(2) : 317-322.

二级参考文献31

  • 1汪承亚,盛瑞兰.细胞凋亡与肿瘤[J].国外医学(生理病理科学与临床分册),1996,16(4):291-293. 被引量:3
  • 2Walter LB. Interleukin-6 delays neutrophil apoptosis via a mechanism involving platelet-activating factor[J]. J Trauma, 1996,40(4) :575.
  • 3Piccip P,Ferrari S, Bacci G,et al. Treatment recommendations for osteosarcomas[J]. Drug, 1994,47:82.
  • 4Rosen G,Tan C, Sanmaneechai A,et al. The rationale for mutiple drug chemotherapy in the teeatment of osteosarcoma[J]. Cancer, 1975,35 (3 Supple) : 936.
  • 5Bacci G,Picci P,Ruggieri P, et al. Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy)for osteosarcoma of the extremities. The istituto Rizzoli experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses)and intraarterial cisplatin[J]. Cancer, 1990,65 : 25.
  • 6Chen D,Zhao M,Mundy GR.Bone morphogenetic proteins.Growth Factors,2004,22(4):233-241
  • 7Kang Q,Sun MH,Cheng H,et al.Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery.Gene Ther,2004,11(17):1312-1320
  • 8Ro TB,Holt RU,Brenne AT,et al.Bone morphogenetic protein-5,-6 and -7 inhibit growth and induce apoptosis in human myeloma cells.Oncogene,2004,23(17):3024-3032
  • 9Kraunz KS,Nelson HH,Liu M,et al.Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer.Br J Cancer,2005,93(8):949-952
  • 10Kim IY,Lee DH,Ahn HJ,et al.Expression of bone morphogenetic protein receptors type-ⅠA,-ⅠB and -Ⅱ correlates with tumor grade in human prostate cancer tissues.Cancer Res,2000,60(11):2840-2844

共引文献26

同被引文献22

  • 1Luu H H,Song W X,Luo X,et al.Distinct roles ol bone morphoge netic proteins in osteogenic differentiation of mesenchymal stem cells [J]. J Orthop Res, 2007,25(5 ) : 665-677.
  • 2Lopez-Coviella I, Mellott T M, Kovacheva V P, et al.Developmental pattern of expression of BMP receptors and Smads and activation of Smadl and Smad5 by BMP9 in mouse basal forebrain[J]. Brain Res, 2006, 1088 ( 1 ) : 49-56.
  • 3Lopez-Coviella I, Follettie M T, Mellott T J, et al. Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons [J]. Proc Natl Acad Sci, 2005, 102(19) : 6984-6989.
  • 4David L,Mallet C,Keramidas M,et al.Bone morphogenetic protein -9 is a circulating vascular quiescence factor[J]. Circ Res, 2008,102( 8 ) : 914-922.
  • 5Scharpfenecker M, van Dinther M, Liu Z, et al. BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis[J]. J Cell Sci., 2007, 120(6 ) : 964-972.
  • 6Ye L, Kynaston H, Jiang W G., et al. Bone morphogenetic protein-9 induces apoptosis in prostate cancer cells, the role of prostate apoptosis response-4[J]. Mol Cancer Res, 2008, 6(10) : 1594-1606.
  • 7Herrera B, Inman G J.A rapid and sensitive bioassay for the simult aneous measurement of multiple bone morphogenetic proteins. Identifi cation and quantification of BMP4, BMP6 and BMP9 in bovine and human serum [J]. BMC Cell Biol, 2009,10(20): 1-11.
  • 8何焕玲,李星星,赖天霞,左国伟,谭启华,周兰.BMP-2、-3、-6和-12在骨肉瘤细胞株中的表达[J].中国组织化学与细胞化学杂志,2007,16(2):134-137. 被引量:9
  • 9左国伟,何焕玲,李星星,赖天霞,王嫣,王胜,周兰.腺病毒介导BMP-2和BMP-6对人骨肉瘤细胞株MG63和U2OS的作用研究[J].第三军医大学学报,2007,29(18):1768-1771. 被引量:8
  • 10Zhang JJ, Ge YL, Sun LE, et AL. Effect of bone morrphogenetic protein-2 on proliferation and apoptosis of gastric cancer ceils [J]. Int J Med Sci, 2012, 9 (2): 184-192.

引证文献2

二级引证文献2

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部