CAJ | 학술논문

目的探讨核因子κB (NF-κB)从细胞质向细胞核移位对食管癌放射治疗的影响.方法采用免疫组化法检测NF-κB在放疗前、后食管鳞癌组织中的表达;采用Western blot和凝胶迁移或电泳迁移率实验检测食管癌细胞系在接受射线照射后NF-κB向细胞核移位情况;以小分子抑制剂SN50阻断NF-κB向细胞核移位,采用克隆形成法评价其对食管鳞癌细胞活性的影响.结果放疗前NF-κB阳性表达的患者与阴性患者的中位生存时间为16和19个月,差异无统计学意义(P＞0.05);放疗后NF-κB阳性表达的患者与阴性患者的中位生存时间为13和35个月,差异有统计学意义(P =0.001).Western blot检测结果显示,在照射治疗后1.5和3h,随着照射剂量的增加,NF-κB蛋白在细胞质中的表达呈现减少的趋势,细胞核中则呈现增加的趋势,而NF-κB蛋白的核质比呈逐渐增加趋势.在照射剂量为0、2、4、12 Gy时,SN50处理组的克隆数分别为96.66、64.66、76.66和10.00个,与对照组比较,差异均有统计学意义(均P＜0.05).结论放射治疗引起了NF-κB从细胞质向细胞核移位,降低了放射治疗食管鳞癌患者的疗效.
목적 탐토핵인자κB (NF-κB)종세포질향세포핵이위대식관암방사치료적영향.방법 채용면역조화법검측NF-κB재방료전、후식관린암조직중적표체;채용Western blot화응효천이혹전영천이솔실험검측식관암세포계재접수사선조사후NF-κB향세포핵이위정황;이소분자억제제SN50조단NF-κB향세포핵이위,채용극륭형성법평개기대식관린암세포활성적영향.결과 방료전NF-κB양성표체적환자여음성환자적중위생존시간위16화19개월,차이무통계학의의(P＞0.05);방료후NF-κB양성표체적환자여음성환자적중위생존시간위13화35개월,차이유통계학의의(P =0.001).Western blot검측결과현시,재조사치료후1.5화3h,수착조사제량적증가,NF-κB단백재세포질중적표체정현감소적추세,세포핵중칙정현증가적추세,이NF-κB단백적핵질비정축점증가추세.재조사제량위0、2、4、12 Gy시,SN50처리조적극륭수분별위96.66、64.66、76.66화10.00개,여대조조비교,차이균유통계학의의(균P＜0.05).결론 방사치료인기료NF-κB종세포질향세포핵이위,강저료방사치료식관린암환자적료효.
Objective To investigate the effect of NF-κB activation on radiation response of esophageal carcinoma.Methods The expression of NF-κB was detected in pretreatment and posttreatment specimens of patients with ESCC by immunohistochemistry.Electrophoretic mobility shift assay (EMSA) and Western blot were used to detect the activation of NF-κB in esophageal cancer cell line KYSE150 cells.SN50,a specific NF-κB inhibitor,was applied to inhibit the activation of NF-κB.Clone formation test was used to detect the radiosensitivity of esophageal cancer cells.Results The median survival time of patients with activated and inactivated NF-κB in the pretreatment specimens were 16 and 19 months,respectively,with a non-significant difference between the two groups (P ＞ 0.05).As to the patients with activated and inactivated NF-κB in posttreatment specimens,the median survival times were 13 and 35 months,respectively,with a significant difference (P ＜ 0.01) between them.Western blot showed that the cytoplasmic expression of NF-κB was reduced with increasing radiation dose at 1.5 and 3 hours after radiation treatment.However,the expression of NF-κB in the cell nuclei was increased under the same condition,showing a trend of increased nucleus/cytoplasm ratio.The clone number in SN50 group was 96.66,64.66,76.66 and 10.00 under 0,2,4 and 12 Gy irradiation,which demonstrated a significant difference compared with the control groups (P ＜ 0.001).Conclusions Our results show that activation of NF-κB is induced by radiotherapy.Activation of NF-κB reduces the outcome of radiation treatment of esophageal cancer patients.