白癜风素苷抑制骨肉瘤生长和转移,通过FAK和PI3K / Akt信号通路降低ITGB1表达。
Psoralidin inhibits osteosarcoma growth and metastasis by downregulating ITGB1 expression via the FAK and PI3K/Akt signaling pathways.
发表日期:2023 Mar 31
作者:
Shengwen Cheng, Senrui Liu, Bowen Chen, Chengcheng Du, Pengcheng Xiao, Xuefeng Luo, Li Wei, Yiting Lei, Chen Zhao, Wei Huang
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
冬虫夏草是一种具有药用价值的豆科植物,长期以来被用于治疗各种疾病。白藜芦醇(PSO)是冬虫夏草的主要提取物化合物,并具有抗菌、抗肿瘤、抗炎、抗氧化等药理活性。PSO已经在多种癌症中表现出抑制作用,但是它对骨肉瘤的抑制作用尚未报道。本研究旨在评估PSO对骨肉瘤的抑制作用,并阐明其潜在的分子机制。使用结晶紫、细胞计数试剂盒-8(CCK8)和5-乙炔基-2-脱氧尿嘧啶(EdU)染色试验评估PSO对143B和MG63骨肉瘤细胞增殖的抑制作用。进行划痕愈合和Transwell实验以评估PSO对骨肉瘤细胞迁移和侵袭的影响。使用流式细胞术分析细胞周期和凋亡。为了确定可能的分子机制,进行了RNA测序,并通过Western blotting分析蛋白表达。使用Orthotopic osteosarcoma小鼠模型和免疫组织化学分析评估PSO对骨肉瘤的抑制作用。PSO浓度依赖性地抑制骨肉瘤细胞增殖,抑制细胞迁移和侵袭,并引起细胞周期阻滞和凋亡。在机制上,PSO处理显著抑制了MG63和143B细胞中的载体蛋白酪氨酸激酶(FAK)和磷脂酰肌醇3-激酶(PI3K)/Akt信号通路,通过下调ITGB1表达。此外,我们证明PSO在体内抑制了骨肉瘤的生长。PSO可能通过下调ITGB1表达抑制FAK和PI3K/Akt信号通路来抑制骨肉瘤。©2023年。作者。
Psoralea corylifolia is a medicinal leguminous plant that has long been used to treat various diseases. Psoralidin (PSO) is the main extract compound of P. corylifolia and exhibits antibacterial, antitumor, anti-inflammatory, antioxidant, and other pharmacological activities. PSO has demonstrated inhibitory effects in several cancers; however, its inhibitory effect on osteosarcoma has not been reported. This study aimed to evaluate the inhibitory effect of PSO on osteosarcoma and elucidate the underlying molecular mechanisms.Crystal violet, cell counting kit-8 (CCK8), and 5-Ethynyl-2'-deoxyuridine (EdU) staining assays were used to assess the inhibitory effect of PSO on the proliferation of 143B and MG63 osteosarcoma cells. Wound healing and Transwell assays were conducted to evaluate the effects of PSO on osteosarcoma cell migration and invasion. The cell cycle and apoptosis were analyzed using flow cytometry. To determine the possible molecular mechanisms, RNA-sequencing was performed and protein expression was analyzed by western blotting. The inhibitory effect of PSO on osteosarcoma in vivo was analyzed using a mouse model of orthotopic osteosarcoma and immunohistochemistry.PSO inhibited osteosarcoma cell proliferation in a concentration-dependent manner, inhibited cell migration and invasion, and induced cell-cycle arrest and apoptosis. Mechanistically, PSO treatment significantly inhibited the focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways by downregulating ITGB1 expression in both MG63 and 143B cells. Furthermore, we demonstrated that PSO restrained osteosarcoma growth in vivo.PSO may suppress osteosarcoma via the FAK and PI3K/Akt signaling pathways by downregulating ITGB1 expression.© 2023. The Author(s).