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Drug Combination Details

General Information of the Combination (ID: C01919)
Name Bufalin   NP Info  + Sorafenib   Drug Info 
Structure +
Disease
Hepatocellular carcinoma [ICD-11: 2C12]
Investigative [1]
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. Enhancing Drug Efficacy by This Combination
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Experiment 1 Reporting the Effect of This Combination [1]
                    Molecule(s)
                    Regulation
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Expression CASP7  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
SMMC-7721 CVCL_0534 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model A total of 1*107 SMMC-7721 cells in a volume of 200 uL PBS were injected into the right flank of each mouse (6-week old male Balb/c nude mice weighing 20 g) to form subcutaneous tumors.
                    Experimental
                    Result(s)
The treatment of sorafenib combined with bufalin synergistically suppressed HCC proliferation and induced apoptosis.
                    Experiment 2 Reporting the Effect of This Combination [2]
                    Molecule(s)
                    Regulation
Down-regulation Expression ERK1  Molecule Info 
Pathway MAP
                    In-vitro Model PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)
Bufalin enhances the anti-proliferative effect of sorafenib on human hepatocellular carcinoma cells through downregulation of ERK.
                    Experiment 3 Reporting the Effect of This Combination [3]
                    Molecule(s)
                    Regulation
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
                    In-vitro Model PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
SMMC-7721 CVCL_0534 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model A total of 5x106 SMMC-7721 cells in 0.2 ml phosphate-buffered saline (PBS) were injected into the right flank of each mouse (six-week old male Balb/c nude mice) to form subcutaneous tumors.
                    Experimental
                    Result(s)
Synergistic anti-hepatoma effect of bufalin combined with sorafenib via mediating the tumor vascular microenvironment by targeting mTOR/VEGF signaling.
                    Experiment 4 Reporting the Effect of This Combination [4]
                    Molecule(s)
                    Regulation
Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
                    In-vitro Model HUVEC CVCL_2959 Healthy Homo sapiens
                    Experimental
                    Result(s)
Bufalin enhances anti-angiogenic effect of sorafenib via AKT/VEGF signaling.
    β. Reversing Drug Resistance by This Combination
                 Reversing Drug Resistance     Click to Show/Hide
                    Experiment 1 Reporting the Effect of This Combination [5]
                    Molecule(s)
                    Regulation
Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
Huh-7 CVCL_0336 Adult hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)
Bufalin reverses resistance to sorafenib by inhibiting Akt activation in hepatocellular carcinoma.
References
Reference 1 Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins. Mol Med Rep. 2018 Jun;17(6):8101-8110.
Reference 2 Bufalin enhances the anti-proliferative effect of sorafenib on human hepatocellular carcinoma cells through downregulation of ERK. Mol Biol Rep. 2012 Feb;39(2):1683-9.
Reference 3 Synergistic anti-hepatoma effect of bufalin combined with sorafenib via mediating the tumor vascular microenvironment by targeting mTOR/VEGF signaling. Int J Oncol. 2018 Jun;52(6):2051-2060.
Reference 4 Bufalin enhances anti-angiogenic effect of sorafenib via AKT/VEGF signaling. Int J Oncol. 2016 Mar;48(3):1229-41.
Reference 5 Bufalin Reverses Resistance to Sorafenib by Inhibiting Akt Activation in Hepatocellular Carcinoma: The Role of Endoplasmic Reticulum Stress. PLoS One. 2015 Sep 18;10(9):e0138485.
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Cite NPCDR
Visitor Map
Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China