顺铂联合吉西他滨对肺癌PD-1/PD-L1途径的影响  

Effect of cisplatin and gemcitabine on the expression of PD-1/PD-L1 pathway in lung cancer

作　　者：孙德彬[1] 留静[2] 

机构地区：[1]浙江省丽水市中心医院呼吸科,浙江丽水323000 [2]浙江省丽水市中心医院急诊科,浙江丽水323000

出　　处：《中国生化药物杂志》2014年第5期50-53,57,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然科学基金(81060006)

摘　　要：目的探讨PD-1/PD-L1途径在肺癌中表达情况及顺铂联合吉西他滨的干预效果。方法将就诊于丽水市中心医院的80例肺癌患者随机分为对照组(A组)、顺铂治疗组(B组)、吉西他滨治疗组(C组)和顺铂联合吉西他滨治疗组(D)组,每组20例,收集各组患者手术切除的肿瘤组织,再以10例良性肺部疾病患者(E组)的手术切除组织作参照,采用Western blot法检测各组组织中PD-1、PD-L1的表达。选择10例同期来医院体检的健康人员(F组)外周血为空白对照,采用流式细胞仪检测B、C、D、F组治疗前后外周血中PD-L1+CD68+巨噬细胞的表达,ELISA法检测B、C、D、F组治疗前后血清中IL-2、IL-4、IL-10的含量。结果 E组PD-1、PD-L1未见表达,A组PD-1、PD-L1的表达较E组上调(P<0.01),B、C、D组较A组显著降低(P<0.05),B、C组比较差异无统计学意义,D组与B、C组相比差异均有统计学意义(P<0.05);B、C、D、F组均可检测到PD-L1+CD68+巨噬细胞的表达,但B、C、D组中PD-L1+CD68+巨噬细胞的比例显著高于F组(P<0.01)。B组和C组均可降低PD-L1+CD68+巨噬细胞的比例(P<0.05),而D组PD-L1+CD68+巨噬细胞比例显著下调(P<0.01)。B、C、D组治疗前外周血血清中IL-2和IL-4含量较F组低(P<0.01),IL-10含量较F组高(P<0.01),治疗后B、C、D组外周血血清中IL-2和IL-4的含量较治疗前均有一定程度的上升(P<0.05),IL-10含量有一定程度的降低(P<0.05)。结论顺铂联合吉西他滨可下调肺癌组织中PD-1/PD-L1的阳性表达率及表达量,降低PD-L1+CD68+巨噬细胞阳性表达,恢复PD-L1对IL-2、IL-4,IL-10所产生的影响,较单独用药效果明显。Objective To investigate the effect of cisplatin and gemcitabine on the expression of PD-1/PD-L1 pathway in lung cancer. Methods 80 cases with lung cancer admitted in lishui central hospital were randomly divided into without chemotherapy group( group A),cisplatin treatment group(group B),gemcitabine group(group C) and cisplatin combined gemcitabine treatment group(group D),each had 20 cases,tumor tissues in each groups were collected by surgical removal. 10 patients with benign lung disease were collected the resected tissues as a reference(E group). The expression of PD-1,PD-L1 in all groups were detected by Western blot assay. 10 healthy people who taking physical examination in our hospital were as blank control(F group). The expression of PD-L1+CD68+macrophages in B,C,D group peripheral blood before and after the treatment were detected by Flow cytometry and the IL-2,IL-4 and IL-10 levels in peripheral blood serum in B,C,D groups before and after treatment were detected by ELISA assay. Results PD-1 and PD-L1 were not expression in group E. Compared with group E,the expression of PD-1 and PD-L1 were upregulated in group A(P < 0. 01); compared with group A,the expression of PD-1 and PD-L1 were down-regulated in B、C、D group. There was no difference between B and C group,the expression of PD-1 and PD-L1 in group D were lower than B,C group( P < 0. 05). The expression of PD-L1+CD68+macrophages could be detected in B,C,D,F group,and its expression in group F was significantly lower than the other groups( P <0. 01). The rate of PD-L1+CD68+macrophages in both B group and C group were reduced significantly(P < 0. 05),and in group D was more( P <0. 01). The IL-2 and IL-4 levels in peripheral blood serum in B,C,D group before the treatment were lower than F group(P < 0. 01),while the IL-10 level was higher than F group(P < 0. 01). After the treatment,the IL-2 and IL-4 levels in peripheral blood serum of B,C,D group were up-regulated in a certain degree(P < 0. 05),but IL-10 levels have a certain degree of reduction(

关 键 词：肺癌 顺铂 吉西他滨 PD-1/PD-L1途径 

分 类 号：R738.1[医药卫生—肿瘤]