Department of Clinical Laboratory, Zhumadian Central Hospital, Zhumadian, 463100, China.
Department of Clinical Laboratory, Zhumadian Central Hospital, Zhumadian, 463100, China.
Biomed Pharmacother. 2019 Nov;119:109399. doi: 10.1016/j.biopha.2019.109399. Epub 2019 Sep 12.
Acute lymphoblastic leukemia (ALL), usually treated with chemotherapy, has limited therapeutic effects and high toxicity. Upregulation of HSP70 induces tumor development, however, the molecular mechanism of HSP70 in ALL remains unclear. In our research, we aimed to investigate the role of HSP70 in ALL, specifically the molecular mechanisms underlying cell apoptosis and proliferation. We found that HSP70 expression in leukomonocytes from ALL patients was increased compared with the control group. HSP70 expression in NALM-6 and BE-13 was also up-regulated contrast with AHH-1. Inhibition of HSP70 significantly promoted cell apoptosis and suppressed cell proliferation in ALL cell lines. Suppression of HSP70 decreased TAK1 and increased Egr-1 protein expression. Further experiments indicated that overexpression of TAK1 ameliorated the effect of HSP70 inhibition on Egr-1 protein expression, cell apoptosis and proliferation. In order to determine whether the effect of HSP70 inhibition on apoptosis and proliferation of ALL cell lines could be achieved via regulation of Egr-1, we performed a loss-of-function experiment for Egr-1. Egr-1 suppression was found to reverse the effect of HSP70 inhibition on cell apoptosis and proliferation in ALL. Taken together, our results suggest that HSP70 inhibition upregulates Egr-1 via TAK1, inducing apoptosis and restricting proliferation in ALL cells.
急性淋巴细胞白血病 (ALL) 通常采用化疗治疗，但疗效有限且毒性较高。HSP70 的上调会诱导肿瘤的发生，但 HSP70 在 ALL 中的分子机制尚不清楚。在我们的研究中，我们旨在研究 HSP70 在 ALL 中的作用，特别是细胞凋亡和增殖的分子机制。我们发现，与对照组相比，ALL 患者白细胞中的 HSP70 表达增加。NALM-6 和 BE-13 中的 HSP70 表达也上调，而 AHH-1 则下调。抑制 HSP70 可显著促进 ALL 细胞系中的细胞凋亡并抑制细胞增殖。抑制 HSP70 可降低 TAK1 并增加 Egr-1 蛋白表达。进一步的实验表明，过表达 TAK1 可改善 HSP70 抑制对 Egr-1 蛋白表达、细胞凋亡和增殖的影响。为了确定 HSP70 抑制对 ALL 细胞系凋亡和增殖的影响是否可以通过调节 Egr-1 来实现，我们对 Egr-1 进行了功能丧失实验。结果发现，Egr-1 抑制可逆转 HSP70 抑制对 ALL 细胞凋亡和增殖的影响。综上所述，我们的研究结果表明，HSP70 通过 TAK1 抑制而上调 Egr-1，诱导 ALL 细胞凋亡并限制增殖。
