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作 者:Min Yao Yin Cai Zhi-Jun Wu Ping Zhou Wen-Li Sai De-Feng Wang Li Wang Deng-Fu Yao
机构地区:[1]Research Center of Clinical Medicine,Affiliated Hospital of Nantong University,Nantong 226001,Jiangsu Province,China [2]Department of Medical Immunology,Medical School of Nantong University,Nantong 226001,Jiangsu Province,China [3]Department of Oncology,Xinghua People’s Hospital,Xinghua 225700,Jiangsu Province,China [4]Department of Oncology,Affiliated Nantong Rehabilitation Hospital of Nantong University,Nantong 226002,Jiangsu Province,China [5]Research Center for Intelligent Information Technology,Nantong University,Nantong 226019,Jiangsu Province,China
出 处:《World Journal of Clinical Cases》2022年第28期10017-10030,共14页世界临床病例杂志
基 金:Supported by Projects of the National Natural Science Foundation of China,No.81873915,No.31872738 and No.81673241;Key Plan of Nantong S&T Development,No.MS12020021;Program of Medical School S&T of Nantong University,No.2018YFC0116902。
摘 要:BACKGROUND Insulin-like growth factor-1 receptor(IGF-1R)is over-expressed in hepatocellular carcinoma(HCC).However,the relationship between IGF-1R activation and HCC progression remains unidentified.AIM To investigate the effects of editing IGF-1R on the biological features of HCC cells.METHODS Immunohistochemistry analyzed the expressions of IGF-1R and P-glyco protein(P-gp)in HCC tissues and their distal non-cancerous tissues(non-Ca).IGF-1R was edited with Crispr/Cas9 system,screened specific sg RNAs,and then transfected into Hep G2 cells.CCK-8,scratch wound test detected cell proliferation,migration,invasion and transwell assays,respectively.Alterations of IGF-1R and P-gp were confirmed by Western blotting.Alterations of anti-cancer drug IC_(50)values were analyzed at the cell level.RESULTS The positive rates of IGF-1R(93.6%,χ~2=63.947)or P-gp(88.2%,χ~2=58.448)were significantly higher(P<0.001)in the HCC group than those(36.6%in IGF-1R or 26.9%in P-gp)in the non-Ca group.They were positively correlated between high IGF-1R and P-gp expression,and they were associated with hepatitis B virus infection and vascular invasion of HCC.Abnormal expressions of circulating IGF-1R and P-gp were confirmed and associated with HCC progression.Biological feature alterations of HCC cells transfected with specific sg RNA showed IGF-1R expression down-regulation,cell proliferation inhibition,cell invasion or migration potential decreasing,and enhancing susceptibility of Hep G2 cells to anti-cancer drugs.CONCLUSION Edited oncogenic IGF-1R was useful to inhibit biological behaviors of Hep G2 cells.
关 键 词:Hepatocellular carcinoma Insulin-like growth factor-1 receptor Synergistic effects Multidrug resistance Growth inhibition Biological behaviors
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