桃叶珊瑚苷调节cGAS-STING通路对皮肤鳞状细胞癌细胞放疗敏感性的影响OA

Objective To investigate how aucubin(AUC)regulates the cyclic guanosine monophosphate-adenosine syn-thetase(cGAS)-interferon gene stimulatory protein(STING)pathway and affects radiotherapy sensitivity in cutaneous squamous cell carcinoma(cSCC)cells.Methods Radiotherapy-resistant A431 cells(A431R)was established.A431R cells were divided into negative control(NC)group,radiation group,AUC+radiation group,AUC+radiation+cGAS silencing negative(sh-NC)group,and AUC+radiation+cGAS silencing(sh-cGAS)group.Expression levels of cGAS mRNA and STING mRNA,cell prolif-eration,cell migration and invasion,apoptosis,DNA-dependent protein kinase(DNA-PK),γ-phosphorylated histone H2AX(γ-H2AX)protein expression,cleaved caspase-3,proliferating cell nuclear antigen(PCNA),matrix metalloproteinase 9(MMP-9),and cGAS-STING pathway protein expression were detected.Results Compared with the NC group and radiotherapy group,the AUC+radiotherapy group exhibited elevated cGAS mRNA and STING mRNA,increased apoptosis rate,and higher protein γ-H2AX,cleaved caspase-3,cGAS,and STING in A431R cells,along with reduced OD450 values,colony formation rate,cell migra-tion and invasion capacity,and protein DNA-PK,PCNA,and MMP-9(P＜0.05).Compared with the AUC+radiotherapy+sh-NC group,the AUC+radiotherapy+sh-cGAS group showed decreased cGAS mRNA and STING mRNA,lower apoptosis rate,reducedγ-H2AX and cleaved caspase-3,and decreased cGAS and STING,while demonstrating increased OD450 values,colony formation rate,cell migration and invasion capacity,and DNA-PK,PCNA,and MMP-9(P＜0.05).No statistically significant differences were observed in these parameters between the NC group and radiotherapy group(P＞0.05).Conclusion AUC may enhance ra-diotherapy sensitivity of A431R cells by activating the cGAS-STING pathway,inhibiting cell proliferation,migration,and invasion,and promoting apoptosis.