摘要
目的:基于程序性死亡受体1(programmed death-1,PD-1)介导NF-κB通路探究莪术-三棱对肝癌细胞的影响及作用机制。方法:在体检测各组药物对H22肝癌荷瘤小鼠抑瘤率、脏器指数的影响;对白细胞介素1(interleukin-1,IL-1)、白细胞介素6(interleukin-6,IL-6)及肿瘤坏死因子(tumor necrosis factor-α,TNF-α)水平的影响。运用免疫组化观察瘤组织NF-κBp65、Bcl-2以及Bax蛋白阳性表达。MTT法检测莪术醇、三棱内酯B二者单用及联用对HepG2肝癌细胞的抑制率;蛋白质免疫印迹法检测联合应用对PD-1、NF-κB、Bcl-2、κB抑制因子激酶α/β(inhibitor ofκB kinaseα/β,IKK-α/β)以及核因子κB抑制蛋白α(inhibitor of NF-κB,IκB-α)的影响。结果:体内实验表明,与模型组相比,联合用药能够显著降低瘤质量,能够抑制TNF-α、IL-1和IL-6的表达(其中联合用药高剂量组TNF-α、IL-1和IL-6下降显著),能够抑制瘤组织中NF-κBp65、Bcl-2蛋白的阳性细胞表达率,高表达Bax蛋白。体外实验显示,与模型组相比,联合用药组能显著抑制PD-1、Bcl-2及IKK-α/β蛋白表达,促进NF-κB及IκB-α蛋白表达。结论:联合用药能够显著抑制荷瘤小鼠体内肿瘤的生长,抑制分泌炎症因子,降低或升高NF-κB通路相关蛋白表达,拮抗肝癌细胞增殖。莪术醇以及三棱内脂B联合应用能够提高HepG2细胞增殖抑制率,这一作用可能与PD-1介导的NF-κB通路调控具有相关性。
Objective:Based on programmed death-1(PD-1)-mediated NF-κB pathway,the effect of rhizoma curcumae-rhizoma sparganii on hepatocellular carcinoma cells and its mechanism were explored.Methods:In vivo,the effects of each group of drugs on tumor inhibition rate and organ index of H22 liver cancer-bearing mice were detected.The effects of drugs in each group on the levels of interleukin-1(IL-1),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected.Immunohistochemistry was used to observe the positive expression of NF-κBp65,Bcl-2 and Bax protein in tumor tissues.MTT assay was used to detect the inhibitory rate of curcumol and trigonolactone B alone and in combination on HepG2 liver cancer cells.Western blot was used to detect the effect of combination of drugs on PD-1,NF-κB,Bcl-2,κB kinaseα/β(IKK-α/β)and nuclear factor κB inhibitor α(IκB-α).Results:In vivo experiments showed that compared with the model group,the combination of drugs could significantly reduce the tumour weight,could inhibit the expression of TNF-α,IL-1 and IL-6,of which TNF-α,IL-1 and IL-6 decreased significantly in the high-dose group of the combination of drugs,and could inhibit the positive cellular expression rate of NF-κBp65,Bcl-2 protein,and high expression of Bax protein in the tumour tissue.In vitro experiments showed that compared with the model group,the co-administration group could significantly inhibit the expression of PD-1,Bcl-2 and IKK-α/βproteins and promote the expression of NF-κB and IκB-α proteins.Conclusion:The combination of drugs can significantly inhibit the growth of tumours,inhibit the secretion of inflammatory factors,reduce or elevate the expression of NF-κB pathway-related proteins,and antagonize the proliferation of hepatocellular carcinoma cells in loaded mice.The combined application of curcumol and sparganium lactone B can improve the proliferation inhibition rate of HepG2 cells,which may be related to the regulation of NF-κB pathway mediated by PD-1.
作者
郭洪麟
李静
张琦
崔闻宇
蒋希成
李文兰
张乔
GUO Honglin;LI Jing;ZHANG Qi;CUI Wenyu;JIANG Xicheng;LI Wenlan;ZHANG Qiao(School of Pharmacy,Harbin University of Commerce,Heilongjiang Harbin 150076,China;National Ministry of Education Antitumor Natural Drug Engineering Research Center,Heilongjiang Harbin 150076,China;Heilongjiang Province Primary Laboratory of Drug Research for Prevention and Treatment of Senile Diseases,Heilongjiang Harbin 150076,China;Harbin Nebula Medical Laboratory,Heilongjiang Harbin 150028,China;Heilongjiang University of Chinese Medicine,Heilongjiang Harbin 150040,China)
出处
《现代肿瘤医学》
CAS
2024年第7期1179-1185,共7页
Journal of Modern Oncology
基金
国家自然科学基金(编号:82174261)
黑龙江省中医药管理局中医药项目(编号:ZHY2022-046)。
关键词
莪术-三棱
肝癌
NF-ΚB
PD-1
rhizoma curcumae-rhizoma sparganii
liver cancer
NF-κB
PD-1
