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

作者全名："Cheng, Shengwen; Liu, Senrui; Chen, Bowen; Du, Chengcheng; Xiao, Pengcheng; Luo, Xuefeng; Wei, Li; Lei, Yiting; Zhao, Chen; Huang, Wei"

作者地址："[Cheng, Shengwen; Liu, Senrui; Chen, Bowen; Du, Chengcheng; Xiao, Pengcheng; Luo, Xuefeng; Wei, Li; Lei, Yiting; Zhao, Chen; Huang, Wei] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Lei, YT; Zhao, C; Huang, W (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：CHINESE MEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000960783600001

JCR分区：Q1

影响因子：5.3

年份：2023

卷号：18

期号：1

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结束页：　

文献类型：Article

关键词：Osteosarcoma; Psoralidin; ITGB1; FAK; PI3K; Akt

摘要："BackgroundPsoralea 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.MethodsCrystal 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.ResultsPSO 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.ConclusionPSO may suppress osteosarcoma via the FAK and PI3K/Akt signaling pathways by downregulating ITGB1 expression."

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