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Chlorogenic acid reverses the drug resistance of 5-fluorouracil colon cancer cells by affecting autophagy and drug resistance protein expression
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DOI   10.11656/j.issn.1672-1519.2020.11.22
Key Words   chlorogenic acid;autophagy;drug resistance;colon cancer cell
Author NameAffiliationE-mail
XIONG Gang Department of Emergency, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China  
ZOU Hua Department of Emergency, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China  
HU Chenglian Department of Emergency, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China  
WU Dan Department of Emergency, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China  
DENG Guiliu Department of Emergency, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China 384642953@qq.com 
Abstract
    [Objective] To observe the effect of chlorogenic acid (ChA) on multidrug resistance and autophagy protein in 5-fluorouracil (5-FU)-resistant colon cancer cells (HCT116-R),and to explore the reversal effect of chlorogenic acid on HCT116-R cell line and its related mechanism.[Methods] HCT116 and HCT116-R cells were sub-cultured in vitro,and the effects of ChA and 5-FU on the proliferation of HCT116 cells were detected by CCK8 method. HCT116-R cell line was intervened by 100 mg/L and 400 mg/L ChA for 48 h,and the expression of drug resistance,autophagy related genes and related proteins were analyzed by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western Blot.[Results] ChA can induce 5-FU to inhibit the proliferation of colon cancer HCT116 cells. The results of Western Blot showed that the expressions of p-glycoprotein (P-gp),lung drug resistance related protein (LRP),autophagy related gene Beclin-1 and high mobility group protein B1(HMGB1) in HCT116-R cells were significantly up-regulated compared with those in HCT116 cells (P<0.05). Further analysis showed that ChA inhibited the mrna and protein expressions of P-gp,LRP,Beclin-1 and HMGB1 mRNA HCT116-R cells in a dose-dependent manner (P<0.05),and ChA also decreased the expressions of p-Akt1,Akt1 and mTOR,a mammalian target protein of rapamycin (P<0.05).[Conclusion] ChA decreased the expression of drug resistance related proteins P-gp,LRP and autophagy related proteins Beclin1 and HMGB1 by affecting the activation of Akt1/mTOR molecular pathway,thus reversing the drug resistance of 5-FU colon cancer cell line.

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