ABSTRACT
BACKGROUND@#Tumor recurrence and drug resistance are the main causes of death in tumor patients. The family of acetaldehyde dehydrogenase (ALDH) is closely related to the proliferation, migration, invasion and resistance of tumor cells, and different ALDH subtypes are expressed in different tumor cells. The aim of this study is to elucidate the ALDH subtype in human lung adenocarcinoma HCC-827/GR cells, which resistant to the gefitinib.@*METHODS@#The human lung adenocarcinoma HCC-827 cells were used to generate the gefitinib-resistant HCC-827/GR cells; the expression of ALDH subtype in either HCC-827 or HCC-827/GR was detected by flow cytometry; The proliferative capacity and sensitivity to gefitinib of hcc-827/GR cells were analyzed by MTT assay before and after treatment with 100 μmol/L diethyllaminaldehyde (DEAB); Real-time quantitative PCR was used to detect the expression of ALDH subtypes at mRNA levels in hcc-827 cells and hcc-827/GR cells.@*RESULTS@#Compared with HCC-827 cells, the positive rate of ALDH in HCC-827/GR cells increased. The proliferation ability of HCC-827/GR cells decreased after treatment with 100 μmol/L DEAB. Compared with HCC-827 cells, the expression of ALDH1A1 and ALDH1L1 mRNA was increased in hcc-827/GR cells, but the ALDH3B2 expression was decreased.@*CONCLUSIONS@#ALDH might be used as a molecular biomarker to test the gefitinib-resistant to lung adenocarcinoma cancer cells, and the ALDH1A1 may play a role in gefitinib resistance in lung cancer.
Subject(s)
Humans , Adenocarcinoma , Pathology , Adenocarcinoma of Lung , Aldehyde Oxidoreductases , Genetics , Cell Line, Tumor , Drug Resistance, Neoplasm , Genetics , Enzyme Inhibitors , Pharmacology , Gefitinib , Gene Expression Regulation, Neoplastic , Lung Neoplasms , Pathology , Quinazolines , PharmacologyABSTRACT
OBJECTIVE: To compare the pharmacokinetic parameters between matrine tablets and matrine capsules in healthy volunteers and evaluate the bioequivalence of the two formulations.METHODS: 18 healthy volunteers were assigned to receive matrine tablets(test formulation,600mg) and matrine capsule(reference formulation) respectively q.d on empty stomach.The plasma concentrations of oxymatrine before and after medication were determined by HPLC and the pharmacokinetic parameters(calculated by oxymatrine) were calculated.RESULTS:The pharmacokinetic parameters of matrine tablets vs.matrine capsules in healthy volunteers were as follows:t1/2:(1.51?0.62)h vs.(1.53?0.54)h;Tmax:(1.35?0.13) hvs.(1.29?0.13)h;Cmax:(730.86?101.13)ng?mL-1 vs.(729.58?74.35)ng?mL-1;AUC0～8:(2 579.1?244.4)ng?h? mL-1 vs.(2 505.7?223.5)ng?h?mL-1;AUC0～∞:(2 754.1?331.8)ng?h?mL-1 vs.(2 659.4?253.5)ng?h?mL-1.The relative bioavailability of matrine tablets(calculated by oxymatrine) was(103.7?13.3)%.CONCLUSION: There are no significant differences between matrine tablets and matrine capsule in main pharmacokinetic parameters,which were in conformity with the presumption of bioequivalence between different individuals,different periods or different dosage forms.The two formulations are bioequivalent.