Effect of Aucubin on the radiosensitivity of lung cancer cells by regulating the immune escape mediated by PD-1/PD-L1 signaling pathway
10.3969/j.issn.1673-4130.2024.12.006
- VernacularTitle:桃叶珊瑚苷通过调节PD-1/PD-L1信号通路介导的免疫逃逸对肺癌细胞放疗敏感性的影响
- Author:
Jiefu HE
1
;
Gang DU
;
Fuxing ZHOU
;
Xing LI
Author Information
1. 巴彦淖尔市医院放疗科,内蒙古巴彦淖尔 015000
- Keywords:
Aucubin;
programmed death-1/programmed death ligand-1 signaling pathway;
lung canc-er;
immune escape;
radiosensitivity
- From:
International Journal of Laboratory Medicine
2024;45(12):1435-1441
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the Aucubin by regulating programmed death-1(PD-1)/programmed death ligand-1(PD-L1)signaling pathway mediated immune escape the influence of radiation sensitivity on the lung cancer cells and its mechanism of action.Methods Human lung cancer cell line NCI-H1299 was trea-ted with 0-300 μmol/mL Aucubin,and cell viability was detected by MTT assay.Cells were divided into nor-mal control group(Control group),radiotherapy group(6 Gy group),Aucubin group,Aucubin+radiotherapy group(Aucubin+6 Gy group).Cell proliferation were detected by colony formation assay and Edu assay.Cell apoptosis was detected by flow cytometry.The levels of tumor necrosis factor-α(TNF-α),interferon-y(IFN-y)and interleukin(IL)-2 in the supernatant of cell culture medium were detected by enzyme-linked immu-nosorbent assay(ELISA).The protein expressions of PD-1 and PD-L1 were detected by Western blot.A mouse model of lung cancer xenograft was established and divided into Control group,radiotherapy group(5 Gy group),Aucubin group,and Aucubin+5 Gy group.The volume and mass of transplanted tumor were measured.ELISA was used to detect the levels of TNF-α,IFN-y,and IL-2,and Western blot was used to de-tect the protein expressions of PD-1 and PD-L1.Results Compared with 0 μmol/mL Aucubin,25-125μmol/mL Aucubin could reduce cell viability,and 100 μmol/mL aucubin was selected for subsequent experi-ments.Compared with the Control group,cell clone formation number,Edu positive rate,TNF-α level,PD-1 and PD-L1 protein expression levels were significantly decreased(P＜0.05),and the apoptosis rate,IFN-γ and IL-2 levels were significantly increased(P＜0.05)in the 6 Gy group and the Aucubin group.Compared with the 6 Gy group and Aucubin group,the Aucubin+6 Gy group had significantly lower cell colony formation number,Edu positive rate,TNF-α level,PD-1 and PD-L1 protein expression levels(P＜0.05),and significant-ly higher apoptosis rate,IFN-γ and IL-2 levels(P＜0.05).Compared with the Control group,the trasplanted tumor volume and weight,TNF-α level and PD-1 and PD-L1 protein expression levels in the 5 Gy group and Aucubin group were decreased(P＜0.05),while IFN-γ and IL-2 levels were increased(P＜0.05).Compared with the 5 Gy group and Aucubin group,the Aucubin+5 Gy group had significantly lower transplanted tumor volume and mass,TNF-α level and PD-1 and PD-L1 expression levels(P＜0.05),and significantly higher IFN-γ and IL-2 levels(P＜0.05).Conclusion Aucubin may enhance the radiosensitivity of lung cancer cells by blocking the immune escape mediated by PD-1/PD-L1 signaling pathway.
