發(fā)布時(shí)間：2018-11-15 21:58

【摘要】：目的:探討細(xì)胞周期蛋白依賴性激酶4/6(cyclin-dependent kinases 4/6,CDK4/6)靶向抑制劑PD0332991在套細(xì)胞淋巴瘤(mantle cell lymphoma,MCL)集落形成中的作用及機(jī)制。方法:采用流式細(xì)胞術(shù)檢測(cè)PD0332991對(duì)MCL細(xì)胞周期的影響;應(yīng)用Western blot法檢測(cè)PD0332991處理后MCL細(xì)胞Rb蛋白和磷酸化Rb(phosphorylated retinal blastoma,p-Rb)蛋白的表達(dá)水平;采用集落形成實(shí)驗(yàn)檢測(cè)PD0332991、米托蒽醌及雙藥聯(lián)合對(duì)MCL細(xì)胞集落形成能力的影響。結(jié)果:采用流式細(xì)胞術(shù)研究證實(shí)PD0332991使G0/G1期MCL細(xì)胞明顯增多,而S期細(xì)胞明顯下降,導(dǎo)致細(xì)胞的G0/G1期阻滯。應(yīng)用Western blot法檢測(cè)顯示PD0332991對(duì)Rb蛋白表達(dá)無(wú)影響,但能明顯下調(diào)磷酸化Rb蛋白的水平。集落形成實(shí)驗(yàn)顯示PD0332991可抑制MCL細(xì)胞集落形成,并增強(qiáng)米托蒽醌對(duì)MCL集落形成的抑制作用。結(jié)論:CDK4/6靶向抑制劑PD0332991可通過(guò)抑制MCL細(xì)胞Rb蛋白磷酸化,導(dǎo)致細(xì)胞的G0/G1期阻滯,增強(qiáng)米托蒽醌抑制MCL集落形成的能力。
[Abstract]:Aim: to investigate the role and mechanism of cyclin-dependent kinases 4 / 6 (cyclin-dependent kinases 4 / 6) -targeted inhibitor PD0332991 in colony formation of (mantle cell lymphoma,MCL. Methods: the effect of PD0332991 on MCL cell cycle was detected by flow cytometry, and the expression of Rb protein and phosphorylated Rb (phosphorylated retinal blastoma,p-Rb protein in MCL cells treated with PD0332991 were detected by Western blot assay. The effect of PD0332991, mitoxantrone and combination of two drugs on the colony forming ability of MCL cells was detected by colony forming assay. Results: flow cytometry was used to demonstrate that PD0332991 significantly increased the number of MCL cells in G0/G1 phase, while the S phase cells decreased, resulting in cell arrest in G0/G1 phase. Western blot assay showed that PD0332991 had no effect on the expression of Rb protein, but could significantly down-regulate the level of phosphorylated Rb protein. Colony formation assay showed that PD0332991 could inhibit the colony formation of MCL cells and enhance the inhibitory effect of mitoxantrone on MCL colony formation. Conclusion: CDK4/6 targeting inhibitor PD0332991 can inhibit the phosphorylation of Rb protein in MCL cells, resulting in cell G0/G1 phase arrest and enhance the ability of mitoxantrone to inhibit MCL colony formation.
【作者單位】： 天津醫(yī)科大學(xué)腫瘤醫(yī)院生物技術(shù)研究室國(guó)家腫瘤臨床醫(yī)學(xué)研究中心天津市腫瘤防治重點(diǎn)實(shí)驗(yàn)室天津市惡性腫瘤臨床醫(yī)學(xué)研究中心天津市腫瘤免疫與生物治療重點(diǎn)實(shí)驗(yàn)室;河北大學(xué)附屬醫(yī)院放射治療科;
【基金】：國(guó)家科技支撐計(jì)劃項(xiàng)目(編號(hào):2015BAI12B12)資助~~
【分類號(hào)】：R733.1

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 紀(jì)小龍,尹彤;套細(xì)胞淋巴瘤[J];診斷病理學(xué)雜志;2000年03期

2 陳忠其;原發(fā)性淋巴結(jié)套細(xì)胞淋巴瘤[J];現(xiàn)代醫(yī)藥衛(wèi)生;2003年11期

3 冀玉靜;;一種可長(zhǎng)期緩解套細(xì)胞淋巴瘤的有效方法[J];國(guó)外醫(yī)學(xué)情報(bào);2003年08期

4 ;套細(xì)胞淋巴瘤的治療現(xiàn)狀和未來(lái)方向[J];河南醫(yī)學(xué)研究;2004年03期

5 楊洪坤;;套細(xì)胞淋巴瘤1例診治體會(huì)[J];基層醫(yī)學(xué)論壇;2006年16期

6 黃文斌;;伴有漿細(xì)胞分化的套細(xì)胞淋巴瘤[J];臨床與實(shí)驗(yàn)病理學(xué)雜志;2006年05期

7 鄭振;熊小亮;;套細(xì)胞淋巴瘤研究進(jìn)展[J];實(shí)用臨床醫(yī)學(xué);2007年04期

8 臧健;李晨;任道凌;易成;;套細(xì)胞淋巴瘤的治療進(jìn)展[J];腫瘤防治研究;2008年06期

9 許改香;童茵;錢潔靖;李穎;金潔;;萬(wàn)珂聯(lián)合楷萊治療復(fù)發(fā)難治套細(xì)胞淋巴瘤1例報(bào)道[J];中國(guó)實(shí)用醫(yī)藥;2008年20期

10 朱軍;應(yīng)志濤;;套細(xì)胞淋巴瘤診治新進(jìn)展[J];中國(guó)腫瘤臨床;2011年18期

相關(guān)會(huì)議論文 前10條

1 萬(wàn)一元;姜文奇;;套細(xì)胞淋巴瘤治療進(jìn)展[A];第四屆中國(guó)腫瘤學(xué)術(shù)大會(huì)暨第五屆海峽兩岸腫瘤學(xué)術(shù)會(huì)議教育集[C];2006年

2 S@永仁;榞祟仁;，

本文編號(hào)：2334514