Combination of metformin and 5-aminosalicylic acid cooperates to decrease proliferation and induce apoptosis in colorectal cancer cell lines

BMC Cancer

Research Article

Samia A. Shouman¹  Mona M. Saber²  Afaf A. Ain-Shoka²  May A. Galal² 

[1] Parmacology Unit,Cancer Biology Department, National Cancer Institute, Cairo University, 11796, Cairo, Egypt;Pharmacology and Toxicolgy Department, Faculty of Pharmacy, Cairo University, 11562, Cairo, Egypt;

关键词: 5-ASA;    Inflammation;    CRC;    NF-κB;    STAT3;    Metformin;   

DOI  :  10.1186/s12885-016-2157-9

 received in 2015-09-03, accepted in 2016-02-10,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe link between inflammation and cancer has been confirmed by the use of anti-inflammatory therapies in cancer prevention and treatment. 5-aminosalicylic acid (5-ASA) was shown to decrease the growth and survival of colorectal cancer (CRC) cells. Studies also revealed that metformin induced apoptosis in several cancer cell lines.MethodsWe investigated the combinatory effect of 5-ASA and metformin on HCT-116 and Caco-2 CRC cell lines. Apoptotic markers were determined using western blotting. Expression of pro-inflammatory cytokines was determined by RT-PCR. Inflammatory transcription factors and metastatic markers were measured by ELISA.ResultsMetformin enhanced CRC cell death induced by 5-ASA through significant increase in oxidative stress and activation of apoptotic machinery. Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1β, IL-6, COX-2 and TNF-α and its receptors; TNF-R1 and TNF-R2. Significant inhibition of activation of NF-κB and STAT3 transcription factors, and their downstream targets was also observed. Metformin also enhanced the inhibitory effect of 5-ASA on MMP-2 and MMP-9 enzyme activity, indicating a decrease in metastasis.ConclusionThe current data demonstrate that metformin potentiates the antitumor effect of 5-ASA on CRC cells suggesting their potential use as an adjuvant treatment in CRC.

【 授权许可】

CC BY   
© Saber et al. 2016