Psoralidin inhibits osteosarcoma growth and metastasis by downregulating ITGB1 expression via the FAK and PI3K/Akt signaling pathways.

Psoralidin inhibits osteosarcoma growth and metastasis by downregulating ITGB1 expression via the FAK and PI3K/Akt signaling pathways.
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DOI:
10.1186/s13020-023-00740-w
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发表时间:
2023-03-31
期刊:
影响因子:
4.9
通讯作者:
Huang, Wei
Huang, Wei
中科院分区:
医学3区
文献类型:
--
作者:
Cheng, Shengwen;Liu, Senrui;Chen, Bowen;Du, Chengcheng;Xiao, Pengcheng;Luo, Xuefeng;Wei, Li;Lei, Yiting;Zhao, Chen;Huang, Wei

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补骨脂是一种豆科药用植物,长期以来一直用于治疗各种疾病。补骨脂素(PSO)是补骨脂的主要提取物,具有抗菌、抗肿瘤、抗炎、抗氧化等药理活性。PSO对多种癌症有抑制作用,但其对骨肉瘤的抑制作用尚未见报道。本研究旨在评价PSO对骨肉瘤的抑制作用,并阐明其分子机制。采用结晶紫、细胞计数试剂盒-8(CCK8)和5-乙炔基-2‘-脱氧尿苷(EDU)染色检测PSO对骨肉瘤细胞143B和MG63的增殖抑制作用。通过创面愈合和Transwell实验评价PSO对骨肉瘤细胞迁移和侵袭的影响。用流式细胞仪分析细胞周期和细胞凋亡率。为了确定可能的分子机制,进行了RNA测序和蛋白质表达的Western blotting分析。采用小鼠原位骨肉瘤模型和免疫组织化学方法,分析了PSO对骨肉瘤的体内抑制作用。PSO以浓度依赖的方式抑制骨肉瘤细胞的增殖,抑制细胞的迁移和侵袭,诱导细胞周期停滞和凋亡。在机制上,PSO通过下调MG63和143B细胞中ITGB1的表达,显著抑制粘着斑激酶(FAK)和磷脂酰肌醇3-激酶(PI3K)/Akt信号通路。此外,我们还证明了PSO在体内对骨肉瘤生长的抑制作用。PSO可能通过下调ITGB1的表达,通过FAK和PI3K/Akt信号通路抑制骨肉瘤生长。网上版载有补充材料,可在10.1186/s13020-023-00740-w查阅。
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. The online version contains supplementary material available at 10.1186/s13020-023-00740-w.
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