SOX7 targeting the ERK1/2/PD-L1 pathway inhibits angiogenesis in colorectal cancer
Objective To investigate the effects and potential mechanisms of SOX7 on the angiogenic func-tions of colorectal cancer cells.Methods Immunofluorescence was applied to detect the expression level of SOX7 in tissue samples from colorectal cancer patients,followed by further study by co-culture of nude mice,human colorectal cancer cell line SW480 cells and human umbilical vein endothelial cells(Human Umbilical Vein Endothe-lial Cells,HUVEC).Western-blot was applied to verify the effect of SOX7 and ERK1/2/PD-L1 on the expression of related proteins in colorectal cancer cells.CCK8 was applied to detect the effect of SOX7 with ERK1/2/PD-L1 on the proliferation of colorectal cancer cells.The effects of SOX7 with ERK1/2/PD-L1 on tumour angiogenesis were deter-mined by endothelial cell tube-forming assay in vitro.Results SOX7 expression was suppressed in human colorec-tal cancer tissues(P＜0.01),while overexpression of SOX7 inhibited tumour growth in mice in vivo(P＜0.01).Over-expression of SOX7 in SW480 cells suppressed the expression of ERK1/2 and c-Jun,and at the same time up-regu-lated the expression of ERK1/2 and c-Jun proteins in SW480 under the action of Senkyunolide I(P＜0.01),an ago-nist of ERK1/2,and reversed the effect of SOX7 on the expression of ERK1/2 and c-Jun proteins in SW480(P＜0.01).In HUVEC,SOX7 inhibited the protein expression of PD-L1,V-EGFR2,p-PI3K and HIF-1α,while Senkyu-nolide I up-regulated the protein expression of PD-L1,V-EGFR2,p-PI3K and HIF-1α in HUVEC.The effect of SOX7 on the expression of the above related proteins in HUVEC was reversed(P＜0.01).PD-1/PD-L1 Inhibitor 3 in-hibited the protein expression of PD-L1,V-EGFR2,PI3K and HIF-1α,while SOX7 overexpression did not show in-hibitory effect under the influence of PD-1/PD-L1 Inhibitor 3.CCK8 results revealed that SOX7 overexpression signif-icantly inhibited the proliferative capacity of HUVEC.The proliferation ability of HUVEC in the two groups under the effect of Senkyunolide I was significantly increased compared with the SOX7 NC group and SOX7 mimic group,and the proliferation ability of HUVEC in the two groups under the effect of PD-1/PD-L1 Inhibitor 3 was significantly de-creased compared with the SOX7 NC group and SOX7 mimic group,all of the above have significant statistical differ-ences(P＜0.01).The results of tube-forming experiments revealed that SOX7 overexpression inhibited angiogenesis in HUVEC,Senkyunolide I strongly accelerated angiogenesis,and PD-1/PD-L1 Inhibitor 3 angiogenesis was signifi-cantly inhibited,all of the above have significant statistical differences(P＜0.01).Conclusion SOX7 inhibits tu-mour proliferation and angiogenesis through the ERK1/2/PD-L1 pathway,and SOX7 may be a potential anti-angio-genic target in the clinical treatment of advanced CRC patients.
Colorectal cancerSRY(sex determining region Y)-box 7(SOX7)Extracellular regulated protein kinases(ERK1/2)Programmed cell death-ligand 1(PD-L1)ProliferationAngiogenesisHuman colorectal cancer cell line SW480 cells
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