A New Strategy for Identifying Mechanisms of Drug-drug Interaction Using Transcriptome Analysis: Compound Kushen Injection as a Proof of Principle
Shen H, Qu Z, Harata-Lee Y, Cui J, Aung TN, Wang W, Kortschak RD, Adelson DL. A New Strategy for Identifying Mechanisms of Drug-drug Interaction Using Transcriptome Analysis: Compound Kushen Injection as a Proof of Principle. Scientific Reports 2019, 9: 15889. PMID: 31685921, PMCID: PMC6828681, DOI: 10.1038/s41598-019-52375-3.Peer-Reviewed Original ResearchConceptsTranscriptome analysisCompound Kushen InjectionCo-expression analysisPotential targetPotential molecular mechanismsTranscriptome dataImportant genesMDA-MB-231 cellsProof of principlePhenotype resultsMolecular mechanismsCytotoxic effectsMetabolic processesMajor regulatorA431 cellsAntagonistic cytotoxic effectsKushen InjectionDNA synthesisCancer cellsInhibition of MyD88GenesComplex herbal mixturesMyD88 geneChemotherapy drugsCancer chemotherapy drugsFractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle
Aung TN, Nourmohammadi S, Qu Z, Harata-Lee Y, Cui J, Shen HY, Yool AJ, Pukala T, Du H, Kortschak RD, Wei W, Adelson DL. Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle. Scientific Reports 2019, 9: 14200. PMID: 31578346, PMCID: PMC6775143, DOI: 10.1038/s41598-019-50271-4.Peer-Reviewed Original ResearchConceptsCompound Kushen InjectionExperimental biology approachesEffect of CKIPlant secondary metabolitesCytokine Signaling PathwaysCKI activityBiology approachReconstitution approachGene expressionCell cyclePhenotype dataSignaling pathwaysSecondary metabolitesBreast cancer cell linesCancer cell linesKushen InjectionSingle major compoundCell linesApoptosisLiquid chromatography fractionationCell viabilityHigh-performance liquid chromatography fractionationMajor compoundsComplex fashionCandidate mechanismAn effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer
Zhang J, Qu Z, Yao H, Sun L, Harata-Lee Y, Cui J, Aung TN, Liu X, You R, Wang W, Hai L, Adelson DL, Lin L. An effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer. Biomedicine & Pharmacotherapy 2019, 118: 109169. PMID: 31310954, DOI: 10.1016/j.biopha.2019.109169.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsAutophagyCarcinoma, Non-Small-Cell LungCell Line, TumorCell SurvivalDown-RegulationDrug Resistance, NeoplasmDrugs, Chinese HerbalGefitinibGene Expression Regulation, NeoplasticHumansLung NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesUp-RegulationConceptsNon-small cell lung cancerCompound Kushen InjectionPI3K/AKT/mTOR pathwayCell lung cancerAKT/mTOR pathwayLung cancerGefitinib treatmentMTOR pathwayFirst-line treatment optionDrug sensitivityPositive EGFR mutationDose-dependent fashionSensitive cell linesMost patientsTreatment optionsEGFR mutationsKushen InjectionTreatment relapseSensitizing agentGefitinibCancerRegulation of autophagyDown regulationTreatment effectsPatients