Zhang Pei-Pei, Wang Yu-Chan, Cheng Chun, Zhang Fei, Ding Da-Zhi, Chen Da-Ke
Department of Oncology, Tongzhou District People's Hospital, Nantong, Jiangsu, 226000, People's Republic of China.
Department of Pathogenic Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
Leuk Res. 2020 May;92:106340. doi: 10.1016/j.leukres.2020.106340. Epub 2020 Mar 9.
Several lines of evidence show that RUNX2 as a transcription factor is closely involved in carcinogenesis in a variety of human cancers. Cell adhesion-mediated drug resistance (CAM-DR) is an important part of the mechanism underlying drug resistance in hematological tumors. In this study, we investigated the biological function of RUNX2 in B-cell Non-Hodgkin's lymphoma (B-NHL) and multiple myeloma (MM). We assessed the expression of RUNX2 in suspension and adhesion model by western blot in B-NHL and MM. Adhesion assay, flow cytometry and CCK-8 were utilized to examine the role and mechanism of RUNX2 in CAM-DR and proliferation in B-NHL and MM. RUNX2 was highly expressed in adherent B-NHL and MM cells compared to suspension cells, and knockdown the expression of RUNX2 could reverse CAM-DR. Besides, RUNX2 could promote the proliferation of B-NHL and MM cells. Furthermore, RUNX2 participated the process of CAM-DR and proliferation by regulating the AKT/GSK-3β pathway. Developing RUNX2 inhibitor may be a possible strategy for drug resistance.
多项证据表明,RUNX2作为一种转录因子,与多种人类癌症的致癌作用密切相关。细胞黏附介导的耐药性(CAM-DR)是血液系统肿瘤耐药机制的重要组成部分。在本研究中,我们调查了RUNX2在B细胞非霍奇金淋巴瘤(B-NHL)和多发性骨髓瘤(MM)中的生物学功能。我们通过蛋白质免疫印迹法评估了RUNX2在B-NHL和MM悬浮及黏附模型中的表达。采用黏附试验、流式细胞术和CCK-8检测RUNX2在B-NHL和MM的CAM-DR及增殖中的作用和机制。与悬浮细胞相比,RUNX2在贴壁的B-NHL和MM细胞中高表达,敲低RUNX2的表达可逆转CAM-DR。此外,RUNX2可促进B-NHL和MM细胞的增殖。此外,RUNX2通过调节AKT/GSK-3β信号通路参与CAM-DR和增殖过程。开发RUNX2抑制剂可能是一种应对耐药性的策略。