Abstract
Aim and Objective: To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action.
Materials and Methods: Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control.
Results: Bioinformatics analysis found that PPI had a total of 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had a good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 μmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01).
Conclusion: The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.
Keywords: Hepatitis B virus-related liver cancer, Polyphyllin I, network pharmacology, molecular docking, apoptosis, primary liver cancer.
Graphical Abstract
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[http://dx.doi.org/10.1016/j.suronc.2016.03.002] [PMID: 27312032]
[http://dx.doi.org/10.1016/S2468-1253(19)30039-1] [PMID: 30902670]
[http://dx.doi.org/10.1016/j.jhep.2017.03.021] [PMID: 28427875]
[http://dx.doi.org/10.1016/j.ctrv.2007.04.001] [PMID: 17512669]
[http://dx.doi.org/10.2144/btn-2018-0100] [PMID: 30091384]
[http://dx.doi.org/10.1007/s11655-009-0316-4] [PMID: 19688324]
[http://dx.doi.org/10.1016/j.biopha.2019.109570] [PMID: 31710893]
[http://dx.doi.org/10.1017/S0031182013000139] [PMID: 23552446]
[http://dx.doi.org/10.1177/0300060519826823] [PMID: 30819018]
[http://dx.doi.org/10.4161/cbt.4.11.2136] [PMID: 16258257]
[PMID: 19300413]
[http://dx.doi.org/10.3390/molecules24112102] [PMID: 31163662]
[http://dx.doi.org/10.3390/molecules21060727] [PMID: 27271583]
[http://dx.doi.org/10.2174/1871520614666140611101040] [PMID: 24917072]
[http://dx.doi.org/10.1080/15376516.2020.1747125] [PMID: 32208876]
[http://dx.doi.org/10.1016/j.phymed.2015.08.014] [PMID: 26598912]
[http://dx.doi.org/10.1155/2018/5241941] [PMID: 30671458]
[http://dx.doi.org/10.1016/j.bmcl.2016.09.005] [PMID: 27623551]
[http://dx.doi.org/10.1016/S1875-5364(13)60037-0] [PMID: 23787177]
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[http://dx.doi.org/10.1016/j.biopha.2021.111612] [PMID: 33915505]
[http://dx.doi.org/10.1056/NEJMra1713263] [PMID: 30970190]
[http://dx.doi.org/10.1038/nrc3449] [PMID: 23344543]
[http://dx.doi.org/10.2147/OTT.S226830] [PMID: 31819506]
[http://dx.doi.org/10.1016/j.taap.2018.07.031] [PMID: 30076870]
[http://dx.doi.org/10.1016/j.jphs.2018.07.008] [PMID: 30119963]
[http://dx.doi.org/10.1016/j.bbrc.2018.02.193] [PMID: 29499193]
[http://dx.doi.org/10.3892/ol.2016.5348] [PMID: 28105203]
[http://dx.doi.org/10.1016/S0254-6272(13)60174-0] [PMID: 24024328]
[http://dx.doi.org/10.18632/oncotarget.14413] [PMID: 28060722]
[http://dx.doi.org/10.1097/MD.0000000000017743] [PMID: 31689825]
[http://dx.doi.org/10.3892/ijo.2018.4464] [PMID: 29956727]
[http://dx.doi.org/10.1016/j.abb.2020.108363] [PMID: 32335049]
[http://dx.doi.org/10.1093/abbs/gmx033] [PMID: 28449039]
[http://dx.doi.org/10.1080/08977194.2018.1473393] [PMID: 29873274]
[http://dx.doi.org/10.1038/s41598-017-06535-y] [PMID: 28740138]
[http://dx.doi.org/10.7150/ijbs.30168] [PMID: 30745853]
[http://dx.doi.org/10.1097/CAD.0000000000000605] [PMID: 29438179]
[http://dx.doi.org/10.1007/978-3-319-53156-4_2] [PMID: 28321811]
[PMID: 2993418]
[http://dx.doi.org/10.1016/j.biopha.2018.09.170] [PMID: 30372868]
[http://dx.doi.org/10.1007/s10620-019-05771-8] [PMID: 31441000]
[http://dx.doi.org/10.1111/febs.14724] [PMID: 30548198]
[PMID: 23070001]
[http://dx.doi.org/10.3892/mmr.2018.8483] [PMID: 29393430]