Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Bioengineered. 2022 Feb;13(2):4428-4440. doi: 10.1080/21655979.2022.2034584.
Diffuse large B-cell lymphoma (DLBCL) is one of the most common causes of cancer death worldwide, and responds poorly to the existing treatments. Thus, identifying novel therapeutic targets of DLBCL is urgently needed. In this study, we found that T-lymphokine-activated killer cell-originated protein kinase (TOPK) was highly expressed in DLBCL cells and tissues. Data from the GEPIA database also indicated that TOPK was highly expressed in DLBCL tissues. The high expression levels of proteins were identified via Western blots and immunohistochemistry (IHC). TOPK knockdown inhibited cell growth and induced apoptosis of DLBCL cells with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium (MTS) and flow cytometry. Further experiments demonstrated that acetylshikonin, a compound that targeted TOPK, could attenuate cell growth and aggravate cell apoptosis through TOPK/extracellular signal-regulated kinase (ERK)-1/2 signaling, as shown by MTS, flow cytometry and Western blots. In addition, we demonstrated that TOPK modulated the effect of acetylshikonin on cell proliferation and apoptosis in U2932 and OCI-LY8 cells using MTS, flow cytometry and Western blots. Taken together, the present study suggests that acetylshikonin suppresses the growth of DLBCL cells by attenuating TOPK signaling, and the targeted inhibition of TOPK by acetylshikonin may be a promising approach for the treatment of DLBCL.
弥漫性大 B 细胞淋巴瘤（DLBCL）是全球癌症死亡的最常见原因之一，对现有治疗方法反应不佳。因此，迫切需要确定 DLBCL 的新治疗靶点。在这项研究中，我们发现 T 淋巴细胞激活的杀伤细胞源性蛋白激酶（TOPK）在 DLBCL 细胞和组织中高度表达。GEPIA 数据库中的数据也表明 TOPK 在 DLBCL 组织中高度表达。通过 Western blot 和免疫组织化学（IHC）鉴定蛋白质的高表达水平。TOPK 敲低抑制 DLBCL 细胞的生长并诱导其凋亡，通过 3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺苯基)-2H-四唑（MTS）和流式细胞术检测。进一步的实验表明，靶向 TOPK 的化合物乙酰紫草素通过 TOPK/细胞外信号调节激酶（ERK）-1/2 信号通路减弱细胞生长并加重细胞凋亡，如 MTS、流式细胞术和 Western blot 所示。此外，我们通过 MTS、流式细胞术和 Western blot 表明，TOPK 调节乙酰紫草素对 U2932 和 OCI-LY8 细胞增殖和凋亡的影响。综上所述，本研究表明乙酰紫草素通过抑制 TOPK 信号抑制 DLBCL 细胞的生长，乙酰紫草素对 TOPK 的靶向抑制可能是治疗 DLBCL 的一种有前途的方法。
