本文選題：全反式維甲酸 + 膠質(zhì)瘤　； 參考：《蘇州大學(xué)》2014年碩士論文

【摘要】：膠質(zhì)瘤是顱內(nèi)腫瘤中發(fā)病率最高的，其發(fā)病機制尚未完全明確，主要的治療方法是手術(shù)加放化療，但并未明顯提高患者的生存時間和生活質(zhì)量。全反式維甲酸(Alltrans retinoic acid, ATRA)在急性早幼粒細(xì)胞白血�。╝cute promyelocytic leukemia，APL）的治療中取得成功，其中ATRA是通過結(jié)合維甲酸受體（Retinoic acid receptor，RAR）發(fā)揮其作用，且ATRA對實體腫瘤的作用也逐漸被發(fā)現(xiàn)。但有關(guān)ATRA作用于膠質(zhì)瘤的研究很少，因此有進(jìn)一步研究的價值。 目的：研究ATRA及維甲酸受體激動劑或拮抗劑對U251膠質(zhì)瘤細(xì)胞增殖和遷移的影響，探討維甲酸受體激動劑或拮抗劑對ATRA抑制U251細(xì)胞增殖的調(diào)節(jié)，為ATRA能作為膠質(zhì)瘤治療的有效藥物提供研究依據(jù)。 方法：(1)使用1、2.5、5、10、20μMATRA分別處理U251細(xì)胞48h，觀察ATRA對U251細(xì)胞的形態(tài)學(xué)變化和細(xì)胞遷移作用的影響，MTT檢測ATRA對細(xì)胞的增殖作用的影響；(2)10μM ATRA分別聯(lián)合四種藥物[維甲酸受體激動劑(RARα激動劑，BMS7531μM)；維甲酸受體拮抗劑(RARα拮抗劑， Ro41-52531μM)；維甲酸受體激動劑(RXRα激動劑，CD32541μM)：④維甲酸受體（RXRα拮抗劑，UVI30031μM）]處理U251細(xì)胞48h，觀察對U251細(xì)胞增殖和遷移的影響，MTT檢測各組對細(xì)胞的增殖作用的影響；(3) Western blot檢測U251細(xì)胞RARa，RXRa的表達(dá)情況。 結(jié)果：(1)細(xì)胞劃痕和MTT顯示，ATRA可以抑制U251細(xì)胞的增殖與遷移，并呈劑量依賴性，ATRA聯(lián)合RARα激動劑BMS753與ATRA組相比，對U251細(xì)胞增殖遷移的抑制作用增強；ATRA聯(lián)合RARα拮抗劑Ro41-5253與ATRA組相比，對U251細(xì)胞增殖遷移的抑制作用減弱。(2) Western blot檢測結(jié)果顯示ATRA可以提高RARα受體蛋白表達(dá)，而對RXRα受體蛋白的作用不明顯，ATRA聯(lián)合RARα激動劑BMS753與ATRA組相比， RARα受體蛋白表達(dá)上升；ATRA聯(lián)合RARα拮抗劑Ro41-5253組與ATRA組相比，RARα受體蛋白表達(dá)下降；ATRA聯(lián)合RXRα激動劑CD3254與ATRA組相比，RXRα受體蛋白表達(dá)上升；ATRA聯(lián)合RXRα拮抗劑UVI3003與ATRA組相比，RXRα受體蛋白表達(dá)量下降。 結(jié)論：上述結(jié)果表明，ATRA對U251細(xì)胞增殖及遷移有抑制作用，這種抑制作用與RARα受體密切相關(guān)；RARα激動劑BMS753可以增強ATRA對U251細(xì)胞的抑制作用，RARα拮抗劑Ro41-5253可以減弱ATRA對U251細(xì)胞的抑制作用，這種作用與RARα受體表達(dá)水平相關(guān)聯(lián)。研究結(jié)果為ATRA用于膠質(zhì)瘤治療的可行性及臨床應(yīng)用中聯(lián)合用藥以減少ATRA的使用量、降低其副作用的發(fā)生提供了依據(jù)。
[Abstract]:Glioma is the highest incidence of intracranial tumors, its pathogenesis is not completely clear, the main treatment is surgery plus radiotherapy and chemotherapy, but has not significantly improved the survival time and quality of life of patients. All trans retinoic acid, ATRA) is successful in the treatment of acute promyelocytic leukemia (APL), in which ATRA plays its role by binding retinoic acid receptor, Retinoic acid receptor rarr, and the effect of ATRA on solid tumors is gradually discovered. However, there are few studies on the effect of ATRA on glioma, so it is valuable to further study. Aim: to investigate the effects of ATRA and retinoic acid receptor agonists or antagonists on the proliferation and migration of U251 glioma cells, and to investigate the effects of ATRA agonists or antagonists on the proliferation of U251 glioma cells. To provide the basis for the study of ATRA as an effective drug for the treatment of glioma. Methods 1) U251 cells were treated with 10 渭 MATRA for 48 hours. The morphological changes of ATRA on U251 cells and the effect of cell migration were observed. The effects of ATRA on proliferation of U251 cells were detected by MTT. The effects of 10 渭 M ATRA combined with four kinds of drugs [retinoic acid receptor] on the proliferation of U251 cells were determined. U251 cells were treated with RXR 偽 agonist (BMS 7531 渭 M), retinoic acid receptor antagonist (Ro41-52531 渭 MN), RXR 偽 agonist (CD32541 渭 M) and RXR 偽 antagonist (UVI 30031 渭 M) for 48 h. The effects of RXR 偽 antagonist on proliferation and migration of U251 cells were observed for 48 h. The expression of RARARXRa in U251 cells was detected by Western blot. Results the cell scratches and MTT showed that ATRA could inhibit the proliferation and migration of U251 cells in a dose-dependent manner, and the inhibitory effect of ATRA combined with RAR 偽 agonist BMS753 on the proliferation and migration of U251 cells was enhanced compared with that of ATRA group and RAR 偽 antagonist Ro41-5253 group. The inhibitory effect on proliferation and migration of U251 cells was attenuated. The results of Western blot analysis showed that ATRA could increase the expression of RAR 偽 receptor protein. But the effect on RXR 偽 receptor protein was not obvious. The expression of RAR 偽 receptor protein increased in ATRA group and RAR 偽 antagonist Ro41-5253 group compared with ATRA group. The expression of RAR 偽 receptor protein in ATRA + RXR 偽 agonist CD3254 and ATRA group was lower than that in ATRA group. Compared with ATRA group, the expression of RXR 偽 receptor protein was increased. The expression of RXR 偽 receptor protein in ATRA combined with RXR 偽 antagonist UVI3003 was lower than that in ATRA group. Conclusion: these results suggest that ATRA can inhibit the proliferation and migration of U251 cells. This inhibitory effect is closely related to RAR 偽 receptor. BMS753 can enhance the inhibitory effect of ATRA on U251 cells. RAR 偽 antagonist Ro41-5253 can attenuate the inhibitory effect of ATRA on U251 cells, which is related to the expression level of RAR 偽 receptor. The results provide a basis for the feasibility of ATRA in the treatment of glioma and the clinical application of combined use of ATRA to reduce the amount of ATRA and to reduce the occurrence of side effects.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R739.41

【參考文獻(xiàn)】

相關(guān)期刊論文 前8條

1 趙廣芬;黃先豹;陳艷;紀(jì)德香;盧瑋;陳穎犁;楊贛萍;陳國安;;急性混合細(xì)胞白血病44例的臨床診治分析[J];實用醫(yī)學(xué)雜志;2012年03期

2 章建軍;蔡琰;;維甲酸受體功能及其在腫瘤治療中的應(yīng)用[J];中國現(xiàn)代應(yīng)用藥學(xué);2010年06期

3 綦斌;譚巖;羅毅男;付雙林;畢春華;田宇;;全反式維甲酸誘導(dǎo)大鼠C6腦膠質(zhì)瘤細(xì)胞凋亡的實驗研究[J];中國腫瘤臨床;2008年01期

4 李華 ,張錦生 ,黃光存 ,張農(nóng) ,陳琦 ,張秀榮;維甲酸核內(nèi)受體β基因轉(zhuǎn)染對大鼠肝星狀細(xì)胞增殖和表型的影響[J];中華肝臟病雜志;2002年04期

5 倪曉凌;靳大勇;許雪峰;樓文暉;王單松;匡天濤;吳文川;戎葉飛;;全反式維甲酸和三氧化二砷協(xié)同誘導(dǎo)胰腺癌細(xì)胞凋亡[J];中華實驗外科雜志;2007年11期

6 閻嶂松;李大鵬;姜爾烈;周春林;劉恩彬;陳輝樹;馮四洲;韓明哲;;全反式維甲酸治療急性早幼粒細(xì)胞白血病并發(fā)Sweet's綜合征(附一例報告并文獻(xiàn)復(fù)習(xí))[J];中華血液學(xué)雜志;2007年07期

7 葉紅;但自力;唐望先;;全反式維甲酸抗腫瘤作用的研究進(jìn)展[J];腫瘤防治研究;2005年12期

8 張敏;胞核內(nèi)維甲酸受體[J];國外醫(yī)學(xué)(生理、病理科學(xué)與臨床分冊);1995年04期

，

本文編號：1970287