PD0332991在套细胞淋巴瘤细胞集落形成中的作用
发布时间：2018-11-15 21:58
【摘要】：目的:探讨细胞周期蛋白依赖性激酶4/6(cyclin-dependent kinases 4/6,CDK4/6)靶向抑制剂PD0332991在套细胞淋巴瘤(mantle cell lymphoma,MCL)集落形成中的作用及机制。方法:采用流式细胞术检测PD0332991对MCL细胞周期的影响;应用Western blot法检测PD0332991处理后MCL细胞Rb蛋白和磷酸化Rb(phosphorylated retinal blastoma,p-Rb)蛋白的表达水平;采用集落形成实验检测PD0332991、米托蒽醌及双药联合对MCL细胞集落形成能力的影响。结果:采用流式细胞术研究证实PD0332991使G0/G1期MCL细胞明显增多,而S期细胞明显下降,导致细胞的G0/G1期阻滞。应用Western blot法检测显示PD0332991对Rb蛋白表达无影响,但能明显下调磷酸化Rb蛋白的水平。集落形成实验显示PD0332991可抑制MCL细胞集落形成,并增强米托蒽醌对MCL集落形成的抑制作用。结论:CDK4/6靶向抑制剂PD0332991可通过抑制MCL细胞Rb蛋白磷酸化,导致细胞的G0/G1期阻滞,增强米托蒽醌抑制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.
【作者单位】： 天津医科大学肿瘤医院生物技术研究室国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心天津市肿瘤免疫与生物治疗重点实验室;河北大学附属医院放射治疗科;
【基金】：国家科技支撑计划项目(编号:2015BAI12B12)资助~~
【分类号】：R733.1
[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.
【作者单位】： 天津医科大学肿瘤医院生物技术研究室国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心天津市肿瘤免疫与生物治疗重点实验室;河北大学附属医院放射治疗科;
【基金】：国家科技支撑计划项目(编号:2015BAI12B12)资助~~
【分类号】：R733.1
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