摘要
目的:探讨二甲双胍对多柔比星诱导的胃癌BGC823细胞衰老相关分泌表型(senescence-associated secretory pheno‐type,SASP)的影响。方法:体外培养人胃癌BGC823细胞,以梯度浓度(50、100、150和200 nmol/L)的多柔比星处理,SA-β-gal染色检测细胞衰老,ELISA检测SASP因子的分泌。在100 nmol/L多柔比星诱导胃癌细胞衰老模型中加入梯度浓度(0、5、10、20 mmol/L)的二甲双胍,观察二甲双胍对多柔比星诱导的细胞衰老、SASP相关因子分泌的影响。结果:随着多柔比星的浓度和处理时间的增加,胃癌BGC823细胞衰老比例呈现先升后降的趋势,以100 nmol/L多柔比星处理96 h后的衰老细胞比例达到峰值(68.7%),伴随SASP相关因子IL-1α、IL-6、IL-8、CXCL1表达的显著增加。在5、10和20 mmol/L的二甲双胍作用下,衰老细胞的比例依次为(55.2±1.9)%、(48.7±2.2)%和(40.8±2.3)%;与单纯诱导衰老组相比,均有显著降低(P<0.01)。同时,随着加入二甲双胍浓度的增加,SASP相关因子IL-1α、IL-6、IL-8和CXCL1的产生均呈现梯度下降的表现。与单纯诱导衰老组相比,IL-6和IL-8在10 mmol/L以上浓度的二甲双胍作用下显著降低(P<0.05或P<0.01),而IL-1α和CXCL1在20 mmol/L二甲双胍作用下显著降低(均P<0.05)。结论:二甲双胍能够抑制多柔比星诱导的胃癌细胞衰老及SASP效应。
Objective:To investigate the effect of metformin on the senescence-associated secretory phenotype(SASP)of doxorubicininduced gastric cancer BGC823 cells.Methods:Human gastric cancer BGC823 cells were cultured in vitro and treated with doxorubicin at gradient concentrations(50,100,150 and 200 nmol/L).Cell senescence was detected by SA-β-gal staining,and SASP factor expression was detected by ELISA.The effects of metformin on cell senescence and SASP factor secretion induced by doxorubicin(100 nmol/L)were observed by adding gradient concentrations of metformin(0,5,10 and 20 mmol/L).Results:With the increase of doxorubicin concentration and treatment time,the senescence rate of gastric cancer BGC823 cells increased first and then decreased.At 96 h after 100 nmol/L doxorubicin treatment,the peak aging rate reached 68.7%,accompanied with significantly increased expressions of SASP factors IL-1a,IL-6,IL-8 and CXCL1.The proportion of senescent cells was(55.2±1.9)%,(48.7±2.2)%and(40.8±2.3)%respectively under the effects of 5,10 and 20 mmol/L metformin,which was significantly lower than that in the non-metformin treatment group(P<0.01).At the same time,with the increase of metformin concentration,the production of SASP factors IL-1α,IL-6,IL-8 and CXCL1 showed a gradient decline.Compared with the non-metformin treatment group,IL-6 and IL-8 decreased significantly under the effect of metformin above 10 mmol/L(P<0.05 or P<0.01),while IL-1αand CXCL1 decreased significantly under the effect of 20 mmol/L metformin(all P<0.05).Conclusion:Metformin can inhibit the senescence and SASP production of gastric cancer cells induced by doxorubicin.
作者
黄禾菁
张鑫
朱振新
卫子然
杨德君
蔡清萍
HUANG Hejing;ZHANG Xin;ZHU Zhenxin;WEI Ziran;YANG Dejun;CAI Qingping(Department of Ultrasound,Changzheng Hospital,Naval Military Medical University,Shanghai 200003,China;Department of Gastrointestinal Surgery,Changzheng Hospital,Naval Military Medical University,Shanghai 200003,China)
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
北大核心
2020年第8期874-878,共5页
Chinese Journal of Cancer Biotherapy
基金
国家自然科学基金资助项目(No.81602617,81773049)
上海长征医院金字塔人才工程国家“优青”后备人才计划资助。
关键词
胃癌
细胞衰老
细胞衰老相关分泌表型
二甲双胍
氧化应激
gastric cancer
cell senescence
senescence-associated secretory phenotype
metformin
oxidative stress
