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 phenotype，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 gastriccancerBGC823cells.Methods:Humangastriccancer BGC823 cells were cultured in vitro and treated with doxorubicin at gradient concentrations(50,100,150and200nmol/L).CellsenescencewasdetectedbySA-β-galstaining,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 sametime,withtheincrease 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 above10mmol/L(P<0.05orP<0.01),whileIL-1αandCXCL1decreasedsignificantlyundertheeffectof20mmol/L metformin (all P<0.05). Conclusion: Metformin can inhibit the senescence and SASPproduction of gastric cancer cells induced by doxorubicin.

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