A Study On Anti-hepatoma Of Tipranavir And Its Related Mechanisms

BackgroundHepatocellular carcinoma(HCC)has a high mortality rate in malignant tumors,which seriously threatens people's health and life.The incidence of HCC is 2 to 8 times higher in men than in women in high-risk areas and low-incidence areas.In Europe and the United States,the main cause of HCC is chronic hepatitis C virus(HCV)infection,while in Asia and Africa it is chronic hepatitis B virus(HBV)infection.At present,the treatment methods of HCC mainly include surgical treatment,ablation technique,transarterial treatment,external electron beam radiotherapy,systemic therapy and systemic therapy.Because surgical treatment has certain limitations and limited methods of adjuvant therapy,there is an urgent need for more effective comprehensive adjuvant therapy to improve the prognosis of patients.Compared with traditional adjuvant methods such as radiotherapy and chemotherapy,molecular targeted drugs can effectively kill tumors.The cells have better curative effect and less systemic side effects,which is of great significance for the treatment of HCC.Silent information reg?Lator 2 homolog 1(SIRT1)is homologous to the silencing information regulator Sir2 gene family found in yeast,and the sirtuin family consists of 7 members(SIRT1-7),which share a highly conserved The catalytic core domain is dependent on the enzyme function of NAD +,and the N-and C-terminal extensions of the family members and their subcellular localization are different.They are responsible for their various binding partners and different metabolic functions,mediating stimulation induction.Apoptosis.SIRT1 deacetylates histones and other key transcriptional regulators such as p53,NF-?B,Foxo,Ku70,E2F1,PPAR? coactivator 1 alpha and hypoxia-inducible transcription factor(HIF).Its extensive influence on gene transcription has been concentrated in cell activities related to cell senescence,metabolism,inflammation and stress response.Studies have shown that SIRT1 is abnormally highly expressed in HCC patients.Therefore,the laboratory developed anti-hepatocarcinoma activity studies based on SIRT1.Research objectiveUsing computer-assisted drug design,this study used the Surflex-Dock module of the Sybyl2.1 platform to study the docking study of Tipranavir and SIRT1 crystals.Through the in vitro anti-hepatocarcinoma activity study,it was preliminarily determined that Tipranavir has a certain inhibitory effect on HepG2 cells,but specifically It is still to be studied which cell pathways inhibit the proliferation of hepatoma cells.Therefore,from this point of view,this study will study the mechanism of action of Tipranavir and provide some ideas for the treatment of HCC by Tipranavir.Research methods1.Molecular docking using Sybyl2.1,the ligand is Tipranavir receptor is SIRT1 protein.2.The anti-hepatocarcinoma activity of Tipranavir in vitro,for example,the effect of drugs on the proliferation of HepG2 cells by MTT assay,the cell proliferation by LDH assay,the apoptosis of hepatocarcinoma cells by flow cytometry,and the cell apoptosis by Hoechst staining Apoptosis-related proteins were detected by death and Western blotting.To construct the SIRT1 silencing cell line of HepG2 cells and verify the effect of SIRT1 gene silencing on apoptosis and apoptosis-related proteins of HepG2 cells.4.The effect of time and dose of Tipranavir on HepG2 cells on SIRT1 protein expression.5.The effect of SIRT1 overexpression on apoptosis of HepG2 cells and its mechanism of action.Research results In this study,Tipranavir was used to inhibit the proliferation of HepG2 cells in vitro by Tipranavir.The expression of Tipranavir was promoted by flow cytometry.Apoptosis was promoted by flow cytometry.HepG2 was silenced by siRNA-SIRT1.SIRT1 thus promotes apoptosis and is verified by the relevant pro-apoptotic proteins that Tipranavir promotes apoptosis by inhibiting SIRT1.