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Validation of quercetin in the treatment of colon cancer with diabetes via network pharmacology, molecular dynamics simulations, and in vitro experiments

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Abstract

This study built a prognostic model for CRC-diabetes and analyzed whether quercetin could be used for CRC-diabetes treatment through a network of pharmacology, molecular dynamics simulation, bioinformatics, and in vitro experiments. First, multivariate Cox proportional hazards regression was used to construct the prognosis modelof CRC-diabetes. Then, the intersection of quercetin target genes with CRC-diabetes genes was used to find the potential target for quercetin in the treatment of CRC-diabetes. Molecular docking and molecular dynamics simulations were used to screen the potential targets for quercetin in the treatment of CRC-diabetes. Finally, we verified the target and pathway of quercetin in the treatment of CRC-diabetes through in vitro experiments. Through molecular docking, seven proteins (HMOX1, ACE, MYC, MMP9, PLAU, MMP3, and MMP1) were selected as potential targets of quercetin. We conducted molecular dynamics simulations of quercetin and the above proteins, respectively, and found that the binding structure of quercetin with MMP9 and PLAU was relatively stable. Finally, according to the results of Western blot results, it was confirmed that quercetin could interact with MMP9. The experimental results show that quercetin may affect the JNK pathway, glycolysis, and epithelial–mesenchymal transition (EMT) to treat CRC-diabetes. Based on the TCGA, TTD, DrugBank, and other databases, a prediction model that can effectively predict the prognosis of colon cancer patients with diabetes was constructed. According to experiment results, quercetin can regulate the expression of MMP9. By acting on the JNK pathway, glycolysis, and EMT, it can treat colon cancer patients with diabetes.

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Funding

This work was supported by the Anhui Provincial Natural Science Foundation (No.:2208085MH240), Quality Engineering Project of Anhui Province (No.:2020jyxm0898; No.:2020jyxm0910), Clinical research project of Anhui Medical University (No.:2020xkj176), and Soft health science research of Anhui province (No.:2020WR01003).

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  1. Weiguo Zhou, Wei Cao and Mingqing Wang have equally contributed to this work.

Authors and Affiliations

  1. Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China

    Weiguo Zhou, Wei Cao, Mingqing Wang, Kang Yang, Xun Zhang, Peng Zhang, Zehua Zhang, Guodong Cao, Bo Chen & Maoming Xiong

  2. School of Public Health, Anhui Medical University, Hefei, 230022, People’s Republic of China

    Yan Liu

  3. Department of Surgery, The People’s Hospital of Hanshan County, Ma’anshan City, Anhui Province, China

    Bo Chen

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Contributions

WZ, WC, MX, BC, and GC designed the idea of the article. WZ, ZZ, and PZ downloaded the data. WZ and KY conducted the bioinformatics analysis of the data. WZ and YL conducted molecular docking. WZ wrote the manuscript.

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Correspondence to Guodong Cao, Bo Chen or Maoming Xiong.

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Zhou, W., Cao, W., Wang, M. et al. Validation of quercetin in the treatment of colon cancer with diabetes via network pharmacology, molecular dynamics simulations, and in vitro experiments. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10725-4

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