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Chlorogenic acid reverses the drug resistance of 5-fluorouracil colon cancer cells by affecting autophagy and drug resistance protein expression |
Hits 1136 Download times 647 Received:May 20, 2020 |
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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 Name | Affiliation | E-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 |
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Abstract
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[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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