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为了研究去乙酰化酶抑制剂TSA诱导MOLT-4细胞周期阻滞和凋亡反应中p21WAFl/Cip-1的表达及其功能, 以组蛋白去乙酰化酶抑制剂TSA处理急性淋巴细胞白血病细胞系MOLT-4,流式细胞仪和细胞吖啶橙染色、瑞士染 色检测细胞周期和凋亡,Western检测p21p21WAFl/Cip-1的表达。结果表明:组蛋白去乙酰化酶抑制剂TSA可有效的诱导 MOLT-4细胞发生G2／M阻滞和凋亡,并且呈现明显的剂量效应关系和时间效应关系;在此周期阻滞与凋亡反应过 程中,p21WAFl/Cip-1蛋白的表达水平在周期阻滞前快速增高,而在凋亡早期开始下降。p21WAFl/Cip-1分子在细胞中的表 达规律与TSA诱导的细胞G2／M阻滞和凋亡反应间存在明显的剂量效应关系和时间效应关系;蛋白酶体抑制剂 MG-132提升p21WAFl/Cip-1分子在细胞中的表达可以增进细胞的G2／M阻滞反应而延缓凋亡。结论:蛋白酶体途径参 与TSA诱导的MOLT-4细胞周期阻滞向凋亡转换过程中p21WAFl/Cip-1分子的降解调控;p21WAFl/Cip-1在TSA诱导的 MOLT-4细胞G2／M阻滞和凋亡反应中起着重要调节作用。
In order to investigate the expression and function of p21WAF1 / Cip-1 in TSA-induced MOLT-4 cell cycle arrest and apoptosis, the acute lymphoblastic leukemia cell line was treated with the histone deacetylase inhibitor TSA MOLT-4, flow cytometry and cell acridine orange staining. Cell cycle and apoptosis were detected by Swiss staining. The expression of p21p21WAF1 / Cip-1 was detected by Western blotting. The results showed that TSA, a histone deacetylase inhibitor, could effectively induce G2 / M arrest and apoptosis in MOLT-4 cells and showed a dose-response and time-effect relationship. The cycle arrest and apoptosis During the reaction, the expression level of p21WAF1 / Cip-1 protein rapidly increased before the cycle arrest, but decreased at the early stage of apoptosis. The expression of p21WAF1 / Cip-1 in cells and the TSA-induced G2 / M arrest and apoptosis were significantly dose-dependent and time-dependent. The proteasome inhibitor MG-132 enhanced the expression of p21WAF1 / Cip- 1 molecule expression in cells can promote G2 / M arrest in cells and delay apoptosis. CONCLUSION: The proteasome pathway is involved in the degradation of p21WAF1 / Cip-1 molecules induced by TSA in MOLT-4 cell cycle and the G2 / M block in MOLT-4 cells induced by TSA And apoptosis play an important regulatory role.