摘要
目的:香菇多糖(Lentinan,LNT)已被证明对癌细胞具有直接的细胞毒性。然而,这种抗肿瘤作用机制尚不清楚。本研究旨在探讨香菇多糖对胰腺癌细胞增殖、迁移及化疗敏感性的影响及其机制。方法:将胰腺癌Capan-1细胞随机分为对照组、IL-6组、IL-6+LNT组,MTT检测细胞存活率,Western blot检测p-STAT3、STAT3、Notch1和Hes1表达水平,Transwell实验检测细胞迁移。建立顺铂耐药细胞模型(Capan-1/DDP),检测各组顺铂半抑制浓度(IC50),分析Ki-67、MMP-9、MRP1和P-gp蛋白相对表达水平。选择Capan-1/DDP细胞株进行裸鼠成瘤实验,验证LNT对裸鼠体内瘤体的瘤重、IL-6/STAT3/Notch信号通路的影响。结果:7.5~240μg/m L香菇多糖对胰腺癌细胞增殖有抑制作用;与IL-6组比较,IL-6+LNT组增殖率显著降低,p-STAT3/STAT3、Notch1和Hes1表达和迁移水平(极)显著下调(P<0.05,P<0.01);与IL-6组比较,IL-6+LNT组Capan-1/DDP细胞株增殖率极显著下调,IC50极显著降低,Ki-67、MMP-9、MRP1和P-gp表达水平显著下调(P<0.05,P<0.01)。体内实验显示,与IL-6组比较,顺铂+IL-6组、LNT+IL-6组瘤体体积、瘤重极显著下调,p-STAT3/STAT3、Notch1、Hes1表达水平(极)显著降低(P<0.05,P<0.01)。结论:LNT抑制胰腺癌Capan-1细胞增殖、迁移和耐药,与调控IL-6/STAT3/Notch信号通路相关。
Objective:Lentinan(LNT)had been shown to have direct cytotoxicity on cancer cells.However,the mechanism of this anti-tumor effect was still unclear.The purpose of this study was to investigate the effect of lentinan on the proliferation,migration and chemosensitivity of pancreatic cancer cells and its mechanism.Methods:Capan-1 cells from pancreatic cancer were randomly divided into control group,IL-6 group and IL-6+LNT group.Cell survival rate was detected by MTT,expression levels of p-STAT3,STAT3,Notch1 and Hes1 were analyzed by Western blot,and cell migration was observed by Transwell test.The cisplatin resistant cell model(Capan-1/DDP)was established,and the semi-inhibitory concentration of cisplatin(IC50)was detected in each group,and the relative expression levels of Ki67,MMP-9,MRP1 and P-gp were analyzed.Capan-1/DDP cell line was selected for tumor formation test in nude mice to verify the effects of LNT on tumor weight and IL-6/STAT3/Notch signaling pathway in nude mice.Results:Lentinan(7.5~240μg/mL)could inhibit proliferation of pancreatic cancer cells.Compared with the IL-6 group,the expression levels of p-STAT3/STAT3,Notch1 and Hes1 in IL-6+LNT group were significantly down-regulated,the proliferation rate and the migration level was significantly dcreased(P<0.05,P<0.01).The proliferation rate of Capan-1/DDP cell line,IC50 and the expression levels of Ki-67,MMP-9,MRP1 and P-gp in IL-6+LNT group were significantly down-regulated(P<0.05,P<0.01).In vivo experiments,compared with IL-6 group,the tumor volume and tumor weight in cisplatin+IL-6 group and LNT+IL-6 group was significantly down-regulated,and expression levels of p-STAT3/STAT3,Notch1 and Hes1 were significantly decreased(P<0.05,P<0.01).Conclusion:LNT inhibits proliferation,migration and drug resistance of Capan-1 pancreatic cancer cells,which is related to the regulation of IL-6/STAT3/Notch signal pathway.
作者
张冬
邓同兴
王丰刚
林小博
程杰西
马永超
ZHANG Dong;DENG Tongxing;WANG Fenggang;LIN Xiaobo;CHENG Jiexi;MA Yongchao*(Luohe Medical College, Luohe 462002, China)
出处
《食品工业科技》
CAS
北大核心
2023年第24期334-340,共7页
Science and Technology of Food Industry
基金
国家自然基金项目(81641180)。
