【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PD0332991對MCL細(xì)胞周期的影響;應(yīng)用Western blot法檢測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;采用集落形成實驗檢測PD0332991、米托蒽醌及雙藥聯(lián)合對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法檢測顯示PD0332991對Rb蛋白表達(dá)無影響,但能明顯下調(diào)磷酸化Rb蛋白的水平。集落形成實驗顯示PD0332991可抑制MCL細(xì)胞集落形成,并增強(qiáng)米托蒽醌對MCL集落形成的抑制作用。結(jié)論:CDK4/6靶向抑制劑PD0332991可通過抑制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)研究室國家腫瘤臨床醫(yī)學(xué)研究中心天津市腫瘤防治重點實驗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實驗室;河北大學(xué)附屬醫(yī)院放射治療科;
【基金】：國家科技支撐計劃項目(編號:2015BAI12B12)資助~~
【分類號】：R733.1

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