首页|Safflower Yellow Inhibits Progression of Hepatocellular Carcinoma by Modulating Immunological Tolerance via FAK Pathway
Safflower Yellow Inhibits Progression of Hepatocellular Carcinoma by Modulating Immunological Tolerance via FAK Pathway
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Objective:To explore the anti-tumor effect of safflower yellow(SY)against hepatocellular carcinoma(HCC)and the underlying potential mechanism.Methods:An in vitro model was established by mixing Luc-Hepa1-6 cells and CD3+CD8+T cells,followed by adding programmed cell death protein 1(PD-1)antibody(Anti-mPD-1)with or without SY.The apoptosis was detected by flow cytometry and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay.The protein levels of programmed cell death 1 ligand 1(PD-L1),chemokine ligand(CCL5),C-X-C motif chemokine ligand 10(CXCL10)were measured by Western blot.An in situ animal model was established in mice followed by treatment with anti-mPD-1 with or without SY.Bioluminescence imaging was monitored with an AniView 100 imaging system.To establish the FAK-overexpressed Luc-Hepa1-6 cells,cells were transfected with adenovirus containing pcDNA3.1-FAK for 48 h.Results:The fluorescence intensity,apoptotic rate,release of inflammatory cytokines,and CCL5/CXCL10 secretion were dramatically facilitated by anti-mPD-1(P＜0.01),accompanied by an inactivation of PD-1/PD-L1 axis,which were extremely further enhanced by SY(P＜0.05 or P＜0.01).Increased fluorescence intensity,elevated percentage of CD3+CD8+T cells,facilitated release of inflammatory cytokines,inactivated PD-1/PD-L1 axis,and increased CCL5/CXCL10 secretion were observed in Anti-mPD-1 treated mice(P＜0.01),which were markedly enhanced by SY(P＜0.05 or P＜0.01).Furthermore,the enhanced effects of SY on inhibiting tumor cell growth,facilitating apoptosis and inflammatory cytokine releasing,suppressing the PD-1/PD-L1 axis,and inducing the CCL5/CXCL10 secretion in Anti-mPD-1 treated mixture of Luc-Hepa1-6 cells and CD3+CD8+T cells were abolished by FAK overexpression(P＜0.01).Conclusion:SY inhibited the progression of HCC by mediating immunological tolerance through inhibiting FAK.
hepatocellular carcinomasafflower yellowChinese medicinetumor microenvironmentprogrammed cell death protein 1focal adhesion kinase
JI Hua-feng、YANG Zi-qiang、HAN Jun-jun、LI He-fang、JIN Zhao-qing、CHEN Wei-qing、CHEN Fei-hua、GONG Mou-chun
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Department of General Surgery,First People's Hospital of Hangzhou Lin'an District,Hangzhou(311300),China
Industry-University Cooperative Education Project of Ministry of Education(2021)
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