二硫代水杨酸/铜通过抑制核因子κB/ B细胞淋巴瘤-6通路诱导对弥漫性大B细胞淋巴瘤的抗肿瘤作用。
DSF/Cu induces antitumor effect against diffuse large B-cell lymphoma through suppressing NF-κB/BCL6 pathways.
作者信息
Zhu Yunying, Lei Chenshuang, Jiang Qian, Yu Qinhua, Qiu Liannv
机构信息
Department of Clinical Laboratory, College of Medical Technology, Zhejiang Chinese Medical University, Hangzhou, 310014, Zhejiang, China.
Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), 158 Shangtang Road, Hangzhou, 310014, Zhejiang, China.
出版信息
Cancer Cell Int. 2022 Jul 26;22(1):236. doi: 10.1186/s12935-022-02661-4.
BACKGROUND
The B-cell lymphoma 6 (BCL6) oncogene is required for the survival of diffuse large B-cell lymphoma (DLBCL), which is incurable using conventional chemotherapy. Thus, it is imperative to improve the survival of patients with DLBCL. Disulfide (DSF) has been shown to have anticancer effects, but its effect on DLBCL remains unclear.
METHODS
Four DLBCL cell lines (OCI-LY1, OCI-LY7, OCI-LY10 and U2932) and primary DLBCL cells from eight newly diagnosed DLBCL patients were pretreated with DSF alone or in combination with Cu. Cell morphology was observed under microscope. Flow cytometry was performed to evaluate the cell apoptosis, cell cycle, the mitochondrial membrane potential and the intracellular accumulation of reactive oxygen species (ROS). The protein expression was respectively measured by flow cytometry and western blotting.
RESULTS
DSF or DSF/Cu exhibited a marked inhibitory effect on the growth of DLBCL cells, accompanied by cell cycle arrest at the G0/G1 phase. Meanwhile, DSF or DSF/Cu significantly induced DLBCL cells apoptosis. Further study revealed that DSF or DSF/Cu promoted apoptosis by inhibiting NF-κB signaling pathway. Interestingly, DSF/Cu significantly reduced BCL6 and AIP levels. In addition, DSF significantly up-regulate p53 protein in OCI-LY7 and OCI-LY10 while down-regulate p53 protein in OCI-LY1 and U2932.
CONCLUSION
These results provided evidence for the anti-lymphoma effects of DSF on DLBCL and suggested that DSF has therapeutic potential to DLBCL.
背景
B细胞淋巴瘤6（BCL6）癌基因是弥漫性大B细胞淋巴瘤（DLBCL）生存所必需的，而DLBCL用传统化疗无法治愈。因此，提高DLBCL患者的生存率势在必行。二硫化物（DSF）已被证明具有抗癌作用，但其对DLBCL的影响仍不清楚。
方法
四种DLBCL细胞系（OCI-LY1、OCI-LY7、OCI-LY10和U2932）以及来自八名新诊断DLBCL患者的原发性DLBCL细胞分别用DSF单独处理或与铜联合处理。在显微镜下观察细胞形态。进行流式细胞术以评估细胞凋亡、细胞周期、线粒体膜电位和细胞内活性氧（ROS）的积累。分别通过流式细胞术和蛋白质印迹法测量蛋白质表达。
结果
DSF或DSF/铜对DLBCL细胞的生长表现出显著的抑制作用，伴随着细胞周期停滞在G0/G1期。同时，DSF或DSF/铜显著诱导DLBCL细胞凋亡。进一步研究表明，DSF或DSF/铜通过抑制NF-κB信号通路促进凋亡。有趣的是，DSF/铜显著降低BCL6和AIP水平。此外，DSF在OCI-LY7和OCI-LY10中显著上调p53蛋白，而在OCI-LY1和U2932中下调p53蛋白。
结论
这些结果为DSF对DLBCL的抗淋巴瘤作用提供了证据，并表明DSF对DLBCL具有治疗潜力。
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