PTBP1通过激活FGFBP1/FGFR1/ERK信号通路降低宫颈癌细胞放疗敏感性OA
PTBP1 reduces radiosensitivity of cervical cancer cells by activating the FGFBP1/FGFR1/ERK signaling pathway
目的 探讨多嘧啶束结合蛋白1(PTBP1)对宫颈癌细胞放疗敏感性的影响,并分析其介导成纤维细胞生长因子结合蛋白1(FGFBP1)的作用机制.方法 将SiHa细胞分为ov-NC组、ov-PTBP1组、ov-PTBP1+sh-NC组和ov-PTBP1+sh-FGFBP1组,SiHa-RR细胞分为sh-NC组、sh-PTBP1组、sh-PTBP1+ov-NC组和sh-PTBP1+ov-FGFBP1组.慢病毒建立稳定转染的细胞;采用CCK-8法、流式细胞术和Transwell实验检测细胞放疗敏感性;采用实时定量PCR检测细胞中PTBP1和FGFBP1 mRNA表达;Western blotting检测细胞中PTBP1、FGFBP1、p-FGFR1和p-ERK1/2蛋白表达.结果 过表达PTBP1增加放射处理的SiHa细胞存活率、迁移和侵袭能力,并降低细胞凋亡率,增加细胞中FGFBP1、p-FGFR1和p-ERK1/2表达;敲减PTBP1能降低放射处理的SiHa-RR细胞存活率、迁移和侵袭能力,并增加细胞凋亡率,降低细胞中FGFBP1、p-FGFR1和p-ERK1/2表达.敲减FGFBP1会降低过表达PTBP1的SiHa细胞存活率、迁移和侵袭能力,并增加细胞凋亡率,下调细胞中p-FGFR1和p-ERK1/2表达;过表达FGFBP1会增加敲减PTBP1的Si-Ha-RR细胞存活率、迁移和侵袭能力,并降低细胞凋亡率,上调细胞中p-FGFR1和p-ERK1/2表达.结论 PTBP1通过上调FGFBP1表达降低宫颈癌细胞对放疗的敏感性,其机制可能与激活FGFR1/ERK信号通路有关.
Objective To investigate the effect of polypyrimidine tract-binding protein 1(PTBP1)on the radiosensitivity of cervical cancer cells and to elucidate the underlying mechanism involving fibroblast growth factor binding protein 1(FGFBP1).Methods SiHa cells were divided into ov-NC,ov-PTBP1,ov-PTBP1+sh-NC and ov-PTBP1+sh-FGFBP1 groups.Radioresistant SiHa(SiHa-RR)cells were divided into sh-NC,sh-PTBP1,sh-PTBP1+ov-NC and sh-PTBP1+ov-FGFBP1.Stable transfection was achieved using lentiviral vectors.Cell radiosensitivity was evaluated using CCK-8 assays,flow cytometry,and Transwell assays.RT-qPCR was used to measure PTBP1 and FGFBP1 mRNA expression levels.Protein expression levels of PTBP1,FGFBP1,p-FGFR1,and phosphorylated ERK1/2(p-ERK1/2)were detected by Western blotting.Results Overexpression of PTBP1 in irradiated SiHa cells increased cell viability,migration,and invasion,decreased apoptosis,and upregulated the expression of FGFBP1,p-FGFR1,and p-ERK1/2.In contrast,PTBP1 knockdown in irradiated SiHa-RR cells reduced cell viability,migration,and invasion,increased apoptosis,and downregulated the expres-sion of FGFBP1,p-FGFR1,and p-ERK1/2.Furthermore,FGFBP1 knockdown in PTBP1-overexpressing SiHa cells reversed these effects,while FGFBP1 overexpression in PTBP1-silenced SiHa-RR cells restored cell viability,migration,and invasion,decreased apoptosis,and increased the expression of p-FGFR1 and p-ERK1/2.Conclusion PTBP1 reduces the radiosensitivity of cervical cancer cells by upregu-lating FGFBP1 expression,potentially by activating the FGFR1/ERK signaling pathway.
李枫;包超恩;刘胤良;曹晓辉;朱晓娅;刘兵;翟福山
河北医科大学第三医院肿瘤科,石家庄 050000河北医科大学第三医院肿瘤科,石家庄 050000河北医科大学第三医院肿瘤科,石家庄 050000河北医科大学第三医院肿瘤科,石家庄 050000河北医科大学第三医院肿瘤科,石家庄 050000河北医科大学第三医院肿瘤科,石家庄 050000河北医科大学第三医院肿瘤科,石家庄 050000
医药卫生
宫颈癌多嘧啶束结合蛋白1成纤维细胞生长因子结合蛋白1放疗敏感性FGFR1/ERK信号通路
cervical cancerpolypyrimidine tract-binding protein 1fibroblast growth factor binding protein 1radiotherapy sensitivityFGFR1/ERK signaling pathway
《中国医科大学学报》 2026 (8)
680-686,7
河北省医学科学研究课题计划(20230092)
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