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Archive > Volume 27 Issue 8 > 2020,27(8):874-878. DOI:10.3872/j.issn.1007-385X.2020.08.006 Prev Next
Basic Research
Metformin inhibits the senescence and senescence-associated secretory phenotype of gastric cancer BGC823 cells induced by doxorubicin
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Abstract:
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.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81602617，81773049), and the National“Excellent Youth”Reserve Talent Plan of “Pyramid Talent Project”of Shanghai Changzheng Hospital
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