大肠杆菌细胞培养上清液在膀胱癌细胞系中的抗癌作用:对炎症调控的新认识。
Anticancer Effects of Cell-Free Culture Supernatant of Escherichia coli in Bladder Cancer Cell Line: New Insight into the Regulation of Inflammation.
发表日期:2023 Sep 12
作者:
Amirreza Mehmandar-Oskuie, Masoud Tohidfar, Bahareh Hajikhani, Forouzan Karimi
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
膀胱癌(BC)是全球发病率排名第十的常见恶性肿瘤,如果未经有效治疗,其病死率和患病率相当高。根据多个研究,炎症环境主要影响膀胱癌的微环境,而细胞因子和趋化因子的长期存在促进了肿瘤的进展。在本研究中,我们探究了大肠杆菌536株培养上清液对膀胱癌模型基因芯片数据(GSE162251)中炎症细胞因子和趋化因子的影响。然后,我们在人类膀胱癌细胞系5637中检验了体外实验结果,以验证和推断研究结果。本研究首次发现,这种化合物对白细胞介素1β(IL-1β),C-C基序趋化因子配体2(CCL2)和C-X3-C基序趋化因子配体1(CX3CL1)的基因表达具有强大的抑制作用,并且在4、8和24小时时增加了NAD(P)H醌脱氢酶1(NQO1)作为抗氧化剂的基因表达。此外,我们证实了在4小时内,膀胱癌细胞系5637中的c-MYC,即MYC原癌基因家族的成员,基因表达下降,并随后在8和24小时内进行了表达跟踪。此外,我们的研究表明,上清液提高了BCL2-Associated X Protein/B细胞淋巴瘤2(BAX/BCL2)比值,并随后的流式细胞术分析证明上清液诱导了细胞凋亡和坏死。最后,我们的研究结果表明,这种化合物是膀胱癌进展抑制的潜在候选物。版权所有 © 2023. Elsevier B.V. 发表。
Bladder cancer (BC) is the 10th most common malignancy in worldwide, with substantial mortality and morbidity if not treated effectively. According to various research, inflammatory circumstances majorly impact the microenvironment of bladder cancer, and the chronic presence of cytokines and chemokines promotes tumor progression. In this investigation, we explored the impact of cell-free culture supernatant ofEscherichia colistrain 536 on inflammatory cytokines and chemokines in bladder cancer model microarray data (GSE162251). Then we examined in silico outcomes on human bladder cancer cell line 5637 to verify and extrapolate findings. This investigation revealed for the first time that this compound has potent suppressor effects on interleukin 1 beta (IL-1β), C-C motif chemokine ligand 2 (CCL2), and C-X3-C motif chemokine ligand 1 (CX3CL1) gene expression as well as increased NAD(P)H quinone dehydrogenase 1 (NQO1), as an anti-oxidant agent, gene expression in 4, 8, and 24 hours. Moreover, we confirmed that c-MYC, a member of the MYC proto-oncogene family, gene expression reduced in 5637 cells in 4 hours and then followed up its expression in 8 and 24 hours. In addition, our investigation demonstrated that the supernatant raised the BCL2-Associated X Protein/B-cell lymphoma 2 (BAX/BCL2) ratio, and subsequent flow cytometry analysis demonstrated that the supernatant induction apoptosis and necrosis. In conclusion, our findings demonstrate that this compound is a potential candidate for the suppression of bladder cancer progression.Copyright © 2023. Published by Elsevier B.V.