苦参碱通过NF-κB信号通路抑制人乳突状卵巢腺癌细胞增殖并诱导其凋亡  

The effect of matrine on proliferation and apoptosis of human papillary ovarian adenocarcinomacells through NF-κB signaling pathway inhibition

作　　者：荆宇洁 杨晓鹃 郝宏霞 JING Yujie;YANG Xiaojuan;HAO Hongxia(Department of Oncology,Linfen People’s Hospital,Linfen,Shanxi 041000,China)

机构地区：[1]临汾市人民医院肿瘤科,山西临汾041000

出　　处：《中国优生与遗传杂志》2023年第10期2027-2033,共7页Chinese Journal of Birth Health & Heredity

摘　　要：目的探讨苦参碱对人乳突状卵巢腺癌(POAC)细胞增殖和凋亡的影响,并研究核转录因子kappa-B(NF-κB)信号通路在其中的作用。方法体外培养POAC细胞株Caov-3,根据不同药物处理,共分为9组:对照组(不用药)、0.5 g/L组(0.5 g/L苦参碱用药)、1.0 g/L组(1.0 g/L苦参碱用药)、1.5 g/L组(1.5 g/L苦参碱用药)、2.0 g/L组(2.0 g/L苦参碱用药)、2.5 g/L组(2.5 g/L苦参碱用药)、阳性对照组(1μg/mL紫杉醇用药)、2.0 g/L+抑制剂组(2.0 g/L苦参碱和20μmol/L BAY11-7082联合用药)和2.0 g/L+激动剂组(2.0 g/L苦参碱和5μmol/L Prostratin联合用药)。分别用细胞计数试剂盒-8、5-乙炔基-2’-脱氧尿苷试剂盒、Hoechst 33258染色试剂盒检测细胞活力、增殖和凋亡;用蛋白免疫印迹法检测蛋白表达。结果与对照组相比,2.0g/L组的相对细胞活力、增殖率和增殖细胞核抗原(PCNA)、磷酸化的NF-κB抑制蛋白alpha(p-IκBα)、磷酸化的NF-κB p65(p-NF-κB p65)的蛋白相对表达量均显著降低(P<0.05),而凋亡率、聚腺苷二磷酸-核糖聚合酶(PARP)大片段的蛋白相对表达量则显著提高(P<0.05)。与2.0 g/L组比较,相对细胞活力、增殖率和PCNA、p-IκBα、p-NF-κBp65的蛋白相对表达量在2.0g/L+抑制剂组均较低,而在2.0g/L+激动剂组均较高(P<0.05),而凋亡率、PARP大片段的蛋白相对表达量在2.0 g/L+抑制剂组较高,而在2.0 g/L+激动剂组则较低(P<0.05)。结论苦参碱可能通过NF-κB通路活化而抑制POAC细胞增殖并诱导其凋亡。Objective To study the effect of matrine on proliferation and apoptosis of human papillary ovarian adenocarcinoma(POAC)cells,and to study the role of nuclear transcription factor kappa-B(NF-κB)signaling pathway.Methods POAC cell line Caov-3 was cultured in vitro and divided into 9 groups:Control group(usage of no medication),0.5 g/L group(usage of 0.5 g/L matrine),1.0 g/L group(usage of 1.0 g/L matrine),1.5 g/L group(usage of 1.5 g/L matrine),2.0 g/L group(usage of 2.0 g/L matrine),2.5 g/L group(usage of 2.5 g/L matrine),positive control group(usage of 1μg/mL paclitaxel),2.0 g/L+inhibitor group(combination usage of 2.0 g/L matrine and 20μmol/L BAY11-7082),2.0 g/L+agonist group(combination usage of 2.0 g/L matrine and 5μmol/L Prostratin).Cell viability,proliferation and apoptosis were detected by cell-counting kit-8,5-acetyne-2'-deoxyuridine kit and Hoechst 33258 staining kit,respectively.Protein expression was detected by western blotting.Results Compared with the control group,relative cell viability,proliferation rate and relative protein levels of proliferating nuclear antigen(PCNA),phosphorylated inhibitor protein of NF-κB alpha(p-IκBα)and phosphorylated NF-κB p65(p-NF-κB p65)in the 2.0 g/L group were significantly decreased(P<0.05),whereas apoptosis rate and relative protein level of poly-ADP-ribose polymerase(PARP)large fragment were significantly increased(P<0.05).Compared with the 2.0 group,relative cell viability,proliferation rate and relative protein levels of PCNA,p-IκBαand p-NF-κB p65 in the 2.0 g/L+inhibitor group were significantly lower(P<0.05),and those in the 2.0 g/L+activator group were significantly higher(P<0.05).Apoptosis rate and PARP large fragment level in the 2.0 g/L+inhibitor group were higher(P<0.05),and those in the 2.0 g/L+activator group were lower than the 2.0 g/L group(P<0.05).Conclusion Matrine inhibited POAC cell proliferation and induced apoptosis through inhibiting NF-κB signaling pathway.

关 键 词：乳突状卵巢腺癌 CAOV-3 核转录因子kappa-B(NF-κB)信号通路 苦参碱 增殖 凋亡 

分 类 号：R285[医药卫生—中药学]