【摘要】：骨肉瘤(Osteosarcoma,OS)是最常見的骨組織原發(fā)惡性腫瘤,并被認(rèn)為是一種分化缺陷性疾病。雖然骨形態(tài)蛋白9(Bone morphogenetic protein 9,BMP9)對間充質(zhì)干細(xì)胞而言,是最強(qiáng)的成骨誘導(dǎo)因子,但其并不能誘導(dǎo)骨肉瘤細(xì)胞的成骨分化。這可能是骨肉瘤的發(fā)病機(jī)制之一。全反式維甲酸(All-trans-retinoic acid,ATRA)能夠成功誘導(dǎo)骨肉瘤細(xì)胞成骨分化;并且在脂肪前體細(xì)胞中,ATRA能增強(qiáng)BMP9所誘導(dǎo)的成骨分化作用。但是ATRA與BMP9在骨肉瘤細(xì)胞中是否具有同樣的作用,尚還不明確。因此,在本文中,我們主要探討這一點(diǎn)。本研究結(jié)果表明:在體外試驗中,BMP9能夠明顯促進(jìn)骨肉瘤143B細(xì)胞的增殖(p0.01),但并不能誘導(dǎo)其成骨分化;ATRA能夠抑制143B細(xì)胞的增殖,并能成功誘導(dǎo)其成骨分化;且ATRA能夠上調(diào)143B細(xì)胞中內(nèi)源性BMP9的表達(dá)水平;過表達(dá)BMP9能夠增強(qiáng)ATRA對143B細(xì)胞增殖及成骨分化的影響;ATRA能夠明顯增強(qiáng)磷酸化p38 MAPK(p-p38)的表達(dá)水平,而單獨(dú)的BMP9卻不能;但當(dāng)BMP9與ATRA聯(lián)用時,過表達(dá)BMP9能夠增強(qiáng)ATRA對p-p38表達(dá)水平的影響;當(dāng)ATRA存在時,BMP9對骨肉瘤143B細(xì)胞的抗增殖和成骨誘導(dǎo)作用均能夠被p38 MAPK抑制劑(SB203580)所減弱(p0.01)。綜上所述,本研究表明,BMP9對骨肉瘤143B細(xì)胞的成骨誘導(dǎo)作用能夠被ATRA恢復(fù),并且二者聯(lián)合的抗增殖作用相比單用ATRA更明顯,而這些均可能與激活p38MAPK信號通路相關(guān)。
[Abstract]:Osteosarcoma (Osteosarcoma OS) is the most common primary malignant tumor of bone tissue and is considered to be a kind of differentiation defect disease. Although bone morphogenetic protein 9 (BMP9) is the strongest osteogenic factor for mesenchymal stem cells, it can not induce osteogenic differentiation of osteosarcoma cells. This may be one of the pathogenesis of osteosarcoma. All trans retinoic acid (All-trans-retinoic) can successfully induce osteogenic differentiation of osteosarcoma cells and enhance the osteogenic differentiation induced by BMP9 in adipose precursor cells. But it is unclear whether ATRA and BMP9 have the same effect in osteosarcoma cells. Therefore, in this article, we mainly discuss this point. The results showed that BMP9 could significantly promote the proliferation of osteosarcoma 143B cells in vitro (p0.01), but it could not induce osteogenic differentiation. ATRA could inhibit the proliferation of 143B cells and induce its osteogenic differentiation successfully. ATRA could up-regulate the expression of endogenous BMP9 in 143B cells, and overexpression of BMP9 could enhance the proliferation and osteogenic differentiation of 143B cells. ATRA could significantly enhance the expression of phosphorylated p38 MAPK (p-p38), but BMP9 alone could not. When combined with BMP9 and ATRA, overexpression of BMP9 could enhance the effect of BMP9 on the expression of p-p38, and the anti-proliferation and osteogenic induction of BMP9 on osteosarcoma 143B cells could be weakened by p38 MAPK inhibitor (SB203580) (p0.01). To sum up, the osteogenesis induced by BMP9 on osteosarcoma 143B cells can be recovered by ATRA, and the anti-proliferation effect of BMP9 is more obvious than that of ATRA alone, which may be related to the activation of p38 MAPK signaling pathway.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R738.1

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 歐陽仁榮,邵念賢,韓潔英,陳芳源 ,鐘璐;STUDY ON EFFECTS OF RED ORPIMENT AND ATRA ON PML GENE AND PROTEIN IN LEUKEMIA CELL LINES[J];Journal of Shanghai Second Medical University;2001年02期

2 賀鵬程;張梅;李靜;蔡瑞波;劉亞琳;曹云新;;Effects of varied interferons in combination with all-trans retinoic acid ( ATRA ) on proliferation and differentiation of ATRA-resistent APL cell[J];Journal of Medical Colleges of PLA;2006年04期

3 殷小華,馮艷,潘波;ATRA DAP方案治療早幼粒細(xì)胞白血病的臨床研究[J];牡丹江醫(yī)學(xué)院學(xué)報;1992年04期

4 黃梅,劉文勵,李春蕊,鄧金牛,周劍鋒,張東華,孫漢英;The Effect of Sodium Butyrate in Combination with ATRA on the Proliferation/Differentiation of SKM-1[J];華中科技大學(xué)學(xué)報(醫(yī)學(xué)英德文版);2004年04期

5 ;Down-Regulation of CD44 Contributes to the Differentiation of HL-60 Cells Induced by ATRA or HMBA[J];Cellular & Molecular Immunology;2007年01期

6 林建樹 ,余英豪;全反視黃酸治療急性早幼粒白血病:初步結(jié)果[J];國外醫(yī)學(xué).輸血及血液學(xué)分冊;1993年03期

7 邰秀珍，云鳳仙;ATRA與化療藥物并用治療急性早幼粒細(xì)胞白血病的臨床觀察[J];內(nèi)蒙古醫(yī)學(xué)院學(xué)報;1994年02期

8 譚立軍,李慧,易靜,湯雪明,沈忠英;EXPERIMENTAL STUDY ON DIMETHYLSULFOXIDEINDUCED DIFFERENTIATION OF HUMAN ESOPHAGEALEPITHELIAL CARCINOMA CELLS[J];Journal of Shanghai Second Medical University;1998年Z1期

9 姜國勝,唐天華,孫關(guān)林,鄔維禮,趙良玉,任海泉,董強(qiáng),任青華,姜楓勤;EFFECT OF ARSENIC TRIOXIDE OR ATRA ON PRIMARY APL CELL OR HL-60 CELLS AND THEIR VALUE ANALYSIS IN HYPERLEUKOCYTOSIS[J];Chinese Journal of Cancer Research;2001年02期

10 姜國勝,唐天華,畢可紅,張玉昆,任海泉,姜楓勤,任青華,真剛,劉傳芳,彭軍,郭桂月,劉秀蘭,田志剛;CYTOKINE SECRETION IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA AFTER TREATMENT WITH ALLTRANS RETINOIC ACID[J];Chinese Journal of Cancer Research;2003年01期

相關(guān)會議論文 前10條

1 ;ATRA Supresses KLF4 Deacetylation Via Inhibiting Its Interaction with HDAC2 in VSMCs[A];2008年全國生物化學(xué)與分子生物學(xué)學(xué)術(shù)大會論文摘要[C];2008年

2 鄭培p，

本文編號：2129534