| Background:Non-Small Cell Lung Cancer(NSCLC)is the most common histological subtype of lung cancer,accounting for more than 90%,and has become one of the important public health issues worldwide.The main treatments include surgery,chemotherapy,radiotherapy,targeted therapy and immunotherapy.The combined application of these treatments has achieved acceeptable clinical efficacy,but has high side effects and is often accompanied by adverse outcomes such as metastasis,recurrence and poor prognosis.The pathogenesis of NSCLC has not been completely clarified,and exploring targets for its pathogenesis and progression is a hot issue in targeted therapy of NSCLC.Therefore,the development and research of anti-tumor drugs with low toxic effects and high biological activity can solve this problem in a targeted manner and have become one of the important research directions.In recent years,with the continuous deepening of research,the anti-tumor effects of the active ingredients of traditional Chinese medicine have attracted more and more attention from scholars and become a research hotspot;as a means of auxiliary treatment of tumors,they can reduce adverse reactions,increase drug sensitivity,and overcome resistance.It has great advantages in medicine and improving long-term drug efficacy.The main component of the traditional Chinese medicine Cistanche deserticola is Acteoside(ACT),which has anti-inflammatory,antioxidant and anti-tumor effects.Domestic and foreign scholars have found that ACT has anti-proliferation,pro-apoptosis and other anti-tumor effects;but its specific mechanism It is not yet clear whether ACT can improve the effect of small molecule inhibitors in related pathways,thereby affecting the malignant progression of NSCLC.The specific mechanism has not been reported.This study will further explore this scientific issue with a view to providing clinical treatment for NSCLC.Provide laboratory evidence and more therapeutic drug options to promote the development of this field and benefit NSCLC patients.Objective:This study used technologies such as bioinformatics analysis and molecular biology experiments to explore the role and mechanism of ACT targeting the APEX1/MYC axis in regulating NSCLC cell proliferation,apoptosis and migration through in vivo and in vitro experiments.Methods:1.Bioinformatics,network pharmacology and transcriptomic analysis;2.Use CCK-8,plate cloning experiments,Western blot,and other methods to detect the effect of ACT on NSCLC cell viability and proliferation;3.Use Morphological observation flow cytometry,Western blot,immunofluo rescence staining,TUNEL staining and other methods to detect the effect of ACT on NSCLC cell cycle and apoptosis.4.Use scratch experiments and Transwell experiments and other methods to detect the effect of ACT on NSCLC migration ability.5.In vivo experiments use HE staining,IHC,Western blot and other methods to verify that ACT inhibits the growth of transplanted tumors in nude mice.6.siRNA transfection verified that ACT affects NSCLC proliferation,cell cycle,apoptosis and migration through the APEX1 / MYC axis.Results:Different concentrations of ACT affected NSCLC proliferation,cell cycle,apoptosis,and migration through the APEX1 / MYC axis,and amplified the ef fects of 10058-F4 at the same concentration.Conclusions:1.Through network pharmacology,bioinformatics analysis,molecular docking technology and transcriptomic analysis,it was found that ACT has the characteristics of multi-target effects;this study preliminarily anchored the APEX1 / MYC axis as the possible anti-non-small cell lung cancer effect of ACT One of the important signaling pathways and targets.2.In vitro experiments found that ACT can significantly inhibit the vitality,proliferation and migration ability of non-small cell lung cancer cells,leading to cell cycle arrest and inducing apoptosis of non-small cell lung cancer cells.3.In vitro experiments verify that ACT inhibits the proliferation and migration ability of non-small cell lung cancer by targeting the APEX1/MYC axis,leading to cell cycle arrest and inducing apoptosis in the mitochondrial apoptosis pathway.4.ACT has good effectiveness and safety in in vivo experiments on nude mice with non-small cell lung cancer transplanted tumors,and can inhibit the proliferation and migration of transplanted tumors.At the same time,it has been verified that down-regulating the expression of APEX1 / MYC axis can exert an anti-non-small cell lung cancer effect,consistent with the in vitro experimental results. |
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