Influence Of X-ray Irradiation On Expression Of EGFR And PD-L1 And Their Interactions In Esophageal Squamous Carcinoma Cells

Objective: 1.To understand the epidermal growth factor receptor(EGFR)signal transduction pathway whether to regulate the expression of Programmed death ligand 1(PD-L1)in esophageal squamous cell cancer(ESCC)cell lines TE-1 and ECA-109;To explore the regulating effect of cell signal transduction pathways janus kinase 2(JAK2)/signal transducer and activator of transcription 1(STAT1)on the expression of EGFR and PD-L1,and to discuss the possible mechanism of EGFR signaling pathways regulating PD-L1 in ESCC cell lines TE-1 and ECA-109.2.To explore the effect of different dose of radiation combined with EGFR tyrosine kinase inhibitor(EGFR-TKI,Gefitinib)on the expression of PD-L1 in ESCC cell lines,and to provide theoretical support of radiotherapy combined with molecular targeted or immunotherapy for esophageal cancer.Methods: 1.The basic m RNA expression levels of EGFR and PD-L1 in ESCC cell lines TE-1 and ECA-109 were detected by reverse transcription-polymerase chain reaction(RT-PCR).Then,the EGFR and PD-L1 m RNA were detected again after treated with different inhibitors of EGFR signaling pathway(Gefitinib,JAK2-inhibitor,STAT1-inhibitor).2.RT-PCR method was used to assess EGFR and PD-L1 m RNA expression on ESCC cell lines when different doses of X-ray irradiation(0.5Gy?1Gy?1.8Gy?2Gy?6Gy)were conducted on ESCC cell lines TE-1 and ECA-109 combining with gefitinib or not.Results: 1.Between the ESCC cell lines TE-1 and ECA-109,there were differences in the basic EGFR(P <0.01)and PD-L1(P <0.05)m RNA.For TE-1 cell line,the expression of EGFR m RNA was lower than that of ECA-109(P <0.01),but the expression of PD-L1 m RNA was higher than that of ECA-109(P <0.05).2.In ESCC cell lines TE-1 and ECA-109,the expression of EGFR and PD-L1 m RNA was increased significantly by the activation of EGFR signaling pathway and decreased after the use of gefitinib(P<0.01).3.However,the use of JAK2 inhibitor(BMS 911543)or STAT1 inhibitor(Fludarabine)had no significant effect on the expression of PD-L1 m RNA(P >0.05).4.Both EGFR(P < 0.01)and PD-L1(P < 0.01)m RNA expression of ESCC cell lines TE-1 and ECA-109 were increased by X-ray irradiation alone.5.Gefitinib could inhibit the increase of both EGFR m RNA(P <0.01)and PD-L1 m RNA(P <0.01)which was induced by radiation in ECA-109(the initial EGFR m RNA expression was higher than TE-1).In cell line TE-1,the initial EGFR m RNA expression was lower than ECA-109,gefitinib could inhibit the increase of radiation-induced PD-L1 m RNA(P <0.01)and high-dose(>1.8Gy)irradiation induced EGFR m RNA(P <0.01),but it failed to reduce the increase of EGFR m RNA induced by low dose(?1.8Gy)radiation(P >0.05).Conclusion: EGFR signaling pathway is involved in the regulation of PD-L1 expression in ESCC cell lines.Radiation could up-regulate the expression of EGFR and PD-L1 m RNA in ESCC cells which could be inhibited by the use of EGFR-TKI.