摘要
【背景】大量文献报道ω-3多不饱和脂肪酸尤其是二十二碳六烯酸(Docosahexaenoic Acid,DHA)与二十碳五烯酸(Eicosapentaenoic Acid,EPA)具有抗肿瘤作用,但是其抗肿瘤机制还不够完善。【目的】探究ω-3多不饱和脂肪酸、具核梭杆菌以及结直肠癌三者之间的关联。【方法】在检测二十二碳六烯酸、二十碳五烯酸、α-亚麻酸(α-Linolenic Acid,ALA)等ω-3多不饱和脂肪酸对人结直肠腺癌细胞Caco-2、正常结肠上皮细胞NCM460生长影响的基础上,检测DHA等3种多不饱和脂肪酸对具核梭杆菌黏附人体细胞以及Fap2、FadA、RadD等具核梭杆菌毒力关键基因表达的影响。【结果】30μg/mL的DHA、EPA、ALA对Caco-2生长抑制分别为9.09%、4.95%、7.52%,而对NCM460生长抑制达31.15%、25.48%、29.11%,而且相关抑制作用仅具有浓度依赖性而无时间依赖性。经30μg/mL的DHA、EPA、ALA预处理的具核梭杆菌黏附Caco-2细胞的能力分别下降81.04%(P=0)、93.63%(P=0)和68.63%(P=0);而共培养时加入DHA、EPA、ALA对具核梭杆菌黏附Caco-2细胞的能力没有显著影响。同时,30μg/mLDHA处理导致F.nucleatum的Fap2基因显著下降10.22%(P=0.027);30μg/mL EPA处理导致FadA、Fap2基因分别显著下降23.49%(P=0)、15.09%(P=0.003);30μg/mL ALA处理导致FadA基因显著下降26.75%(P=0.012)。【结论】综合上述实验结果以及DHA、EPA、ALA仅能短时间抑制具核梭杆菌生长等文献报道,我们认为,DHA、EPA等ω-3多不饱和脂肪酸并非简单地直接杀伤或抑制肿瘤细胞和F.nucleatum;抑制FadA、Fap2等黏附相关基因表达,降低F.nucleatum黏附宿主细胞能力是其抗肿瘤作用的关键组成部分。ω-3多不饱和脂肪酸等活性物质对F.nucleatum等在结直肠肿瘤发生、发展中发挥重要作用的肠道细菌的影响与机制应深入开展研究。
[Background]The antitumor mechanism ofω-3 polyunsaturated fatty acids represented by DHA and EPA has not been fully investigated.[Objective]To explore the relationship amongω-3 polyunsaturated fatty acids,Fusobacterium nucleatum and colorectal cancer.[Methods]After the suppressive effect ofω-3 polyunsaturated fatty acids(DHA,EPA,ALA)on human colon cancer cell line,Caco-2,and normal colon epithelium cell line,NCM460,was assayed,we investigated the impact of theseω-3 polyunsaturated fatty acids on F.nucleatum,including growth,adhesive ability to Caco-2 cells,and the expression of virulence genes such as Fap2,FadA and RadD.[Results]After treated with 30μg/mL DHA,EPA or ALA respectively,the growth of Caco-2 cells were suppressed 9.09%,4.95%and 7.52%correspondingly,meanwhile the growth of NCM460 cells were suppressed 31.15%,25.48%,29.11%,and only dose-dependent effect was identified.After treated with 30μg/mL DHA,EPA and ALA for 12 hours,the adhesive ability of F.nucleatum to Caco-2 cells was inhibited by 81.04%(P=0),93.63%(P=0)and 68.63%(P=0)respectively,which was consistent with the transcriptive level assay results of FadA,Fap2 in F.nucleatum.The expression of Fap2 was considerably suppressed by 10.22%(P=0.027)after 30μg/mL DHA treatment;FadA,Fap2 were markedly suppressed by 23.49%(P=0)and 15.09%(P=0.003)by 30μg/mL EPA;and for 30μg/mL ALA treatment,FadA was significantly suppressed by 26.75%(P=0.012).[Conclusion]Based on our above results and previous reports that DHA,EPA and ALA only inhibited the growth of F.nucleatum temporally,we proposed thatω-3 polyunsaturated fatty acids i-e EPA and DHA significantly attenuated the adhesive ability of F.nucleatum to host cells via suppressing the expression of adhesion-related genes such as FadA,Fap2,which made major contribution to their antitumor activity,rather than inhibiting the growth of tumor cells and F.nucleatum directly.The effects and mechanisms ofω-3 polyunsaturated fatty acids i-e DHA and EPA on gut bacterium i-e F.nucleatum that play important roles
作者
其力格尔
Sadia Nawab
范殊璇
曹博
李雨昕
田明振
张商浩
马伟
邓子新
BAO Qelger;Sadia Nawab;FAN Shuxuan;CAO Bo;LI Yuxin;TIAN Mingzhen;ZHANG Shanghao;MA Wei;DENG Zixin(Key Laboratory of Microbial Metabolism,School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China;Zhiyuan College,Shanghai Jiao Tong University,Shanghai 200240,China;Shanghai Pinghe School,Shanghai 200000,China)
出处
《微生物学通报》
CAS
CSCD
北大核心
2021年第3期820-829,共10页
Microbiology China
基金
科技部政府间重大专项(2018YFE0102400)。
关键词
Ω-3多不饱和脂肪酸
具核梭杆菌
结直肠癌
黏附
ω-3 polyunsaturated fatty acids
Fusobacterium nucleatum
colorectal cancer
adhesion
