Mechanism of "Pinelliae rhizoma-Arisaematis rhizoma" in treatment of lung cancer based on network pharmacology

Objective:The study was designed to explore the mechanism of“Pinelliae RhizomaArisaematis Rhizoma”(PR-AP)in treatment of lung cancer based on network pharmacology.Methods:The active components and their targets of“Pinelliae Rhizoma-Arisaematis Rhizoma”were screened out from TCMSP database.The cytoscape3.7.0 software was used to construct the drug-active component-targets network.Searched the DisGeNet database to obtain lung cancer related targets.Bisogenet was used to construct"PPI network of active component target"and"PPI network of lung cancer target",and the intersection of the two networks was taken and the target was screened.AutoDockTools software was used to dock the key active ingredients with the key targets.David database was used to perform Go biological process enrichment analysis and KEGG pathway enrichment analysis.Results:A total of 15 active components were collected,including beta-sitosterol,baicalein,Stigmasterol,Cavidine,coniferin,etc.These active components mainly act on 95 key targets such as ESR1 and CDK2,which enriched in multiple lung cancer related signaling pathways,such as PI3KAkt、MAPK、HIF-1、FoxO、TGF-β、Hippo、TNF、Notch、VEGF、cAMP,etc.The results of molecular docking showed that the active components could regulate the core targets(ESR1 and CDK2).Conclusion:The effect of“Pinelliae Rhizoma-Arisaematis Rhizoma”in the treatment of lung cancer embodies the characteristics of multi-component,multi-target and multi-pathway of traditional Chinese medicine.Its mechanism of action may be to play a role in the treatment of lung cancer by regulating cell cycle,angiogenesis,tumor stem cells,etc.This research can provide ideas and references for further research.

Degradation of helicase-like transcription factor(HLTF)byβ-TrCP promotes hepatocarcinogenesis via activation of the p62/mTOR axis

Helicase-like transcription factor (HLTF) has been found to be involved in the maintenance of genome stability and tumoursuppression, but whether its downregulation in cancers is associated with posttranslational regulation remains unclear. Here, weobserved that HLTF was significantly downregulated in hepatocellular carcinoma (HCC) tissues and positively associated with thesurvival of HCC patients. Mechanistically, the decreased expression of HLTF in HCC was attributed to elevated β-TrCP-mediated ubiquitination and degradation. Knockdown of HLTF enhanced p62 transcriptional activity and mammalian target of rapamycin (mTOR)activation, leading to HCC tumourigenesis. Inhibition of mTOR effectively blocked β-TrCP overexpression- or HLTF knockdownmediated HCC tumourigenesis and metastasis. Furthermore, in clinical tissues, decreased HLTF expression was positively correlatedwith elevated expression of β-TrCP, p62, or p-mTOR in HCC patients. Overall, our data not only uncover new roles of HLTF in HCCcell proliferation and metastasis, but also reveal a novel posttranslational modification of HLTF by β-TrCP, indicating that theβ-TrCP/HLTF/p62/mTOR axis may be a new oncogenic driver involved in HCC development. This finding provides a potentialtherapeutic strategy for HCC patients by targeting the β-TrCP/HLTF/p62/mTOR axis.