靶向调节性LKB1基因对骨肉瘤细胞增殖和侵袭的抑制作用

Jie Liu
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引用次数: 0

摘要

本研究通过药物干预免疫缺陷裸鼠骨肉瘤异种移植模型,探讨贝沙罗汀对体外培养骨肉瘤细胞系增殖和侵袭的影响。通过生物信息学结合组织芯片研究、转录因子预测结合共表达分析等多种体外实验研究靶向调控基因对骨肉瘤细胞增殖和侵袭的抑制作用,预测骨肉瘤中靶向调控基因的转录因子。RXR蛋白家族、LKB1、AMPK通路、mTOR与机体的免疫调节密切相关。口服贝沙罗汀可抑制骨肉瘤细胞增殖,上调LKB1基因在骨肉瘤活体组织中的表达。本研究采用的免疫缺陷裸鼠异种移植模型,在一定程度上降低了药物靶向LKB1治疗的潜在免疫调节作用。然而,体内过表达LKB1并联合免疫治疗可能成为骨肉瘤的重要免疫治疗途径。LKB1靶向治疗可作为mTOR抑制剂的替代治疗方法之一。
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Inhibitory Effects of Targeted Regulatory LKB1 Gene on the Proliferation and Invasion of Osteosarcoma Cells
In this study, Immunodeficiency Nude Mouse Osteosarcoma Xenograft Model was subjected to the drug intervention to explore the effect of bexarotene on the proliferation and invasion of osteosarcoma cell lines in vitro. The inhibitory effects of targeted regulatory genes on the proliferation and invasion of osteosarcoma cells were studied through various in vitro experiments include bioinformatics combined with tissue microarray research, transcription factor prediction combined with co-expression analysis to predict the transcription factor of targeted regulatory genes in osteosarcoma. The RXR protein family, LKB1, AMPK pathway, and mTOR are closely related to the body’s immune regulation. The oral administration of Bexarotene could inhibit the proliferation and able to up-regulate the expression of LKB1 gene in living osteosarcoma tissue. The xenograft model of immunodeficiency nude mice used in this study was reason for reduced the potential immunoregulatory effect of drug targeted LKB1 therapy to a certain extent. However, overexpression of LKB1 in vivo, and combined immunotherapy may become an important immunotherapy approach for osteosarcoma. LKB1 targeted therapy can potentially be used as one of the alternative treatments for mTOR inhibitors.
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