沉默CCND1基因表达抑制ERK/MAPK信号通路激活提升宫颈癌化疗敏感性

目的 研究CCND1介导ERK/MAPK信号通路介导宫颈癌化疗敏感性的机制.方法 收集60例宫颈癌及癌旁组织标本,qRT-PCR检测组织中CCND1、ERK和MAPK表达量,免疫组化确认并定位CCND1在组织中的表达.筛选宫颈癌细胞株,将细胞分组为Blank组、pcDNA-CCND1组、pcDNA-CCND1 NC组、...

Silencing of CCND1 Gene Expression Inhibiting the Activation of ERK/MAPK Signaling Pathway to Improve the Chemosensitivity of Cervical Cancer

Objective To study the mechanism of CCND1 mediating ERK/MAPK signaling pathway to regulate the chemosensitivity of cervical cancer.Methods The expression of CCND1,ERK and MAPK was detected by qRT-PCR in 60 cervical cancer and adjacent tissues.The expression of CCND1 in tissues was confirmed by immunohistochemistry.With the screening of eligible cell line,cells were transfected and divided into Blank group,pcDNA-CCND1 group,pcDNA-CCND1 NC group,siRNA-CCND1 group,siRNA-CCND1 NC group,SCH772984 group,Honokiol group and siRNA-CCND1+Honokiol group.Furthermore,the expression of CCND1,ERK and MAPK genes and proteins was detected by qRT-PCR and Western blot.CCCK8 was used to detect cisplatin sensitivity of tumor cells and flow cytometry was used to detect apoptosis.Results The expression of CCND1,ERK and MAPK in cervical cancer was higher than that in adjacent tissues(all P<0.05).There was no significant difference in each index among Blank group,pcDNA-CCND1 NC group and siRNA-CCND1 NC group(all P>0.05).Compared with pcDNA-CCND1 NC group,the expression of CCND1,ERK and MAPK gene and protein in pcDNA-CCND1 group increased significantly,while that in siRNA-CCND1 group decreased significantly when compared with siRNA-CCND1 NC group(all P<0.05);and there was a decrease in the expression of CCND1(P<0.05),but no obvious change in the expression of ERK and MAPK when compared with Blank group(all P>0.05).Compared with Blank group,pcDNA-CCND1 group and Honokiol group had increased cisplatin resistance and decreased cell apoptosis(all P<0.05);however,siRNA-CCND1 group and SCH772984 group showed decreased cisplatin resistance and increased cell apoptosis(all P<0.05).While there was no statistical difference in the comparison between siRNA-CCND1+Honokiol group and Blank group(P>0.05).Conclusion CCND1 gene silencing may promote apoptosis of cervical cancer cells and improve chemosensitivity by inhibiting the activation of ERK/MAPK signaling pathway.