A novel kinase inhibitor, LZT-106, downregulates Mcl-1 and sensitizes colorectal cancer cells to BH3 mimetic ABT-199 by targeting CDK9 and GSK-3β signaling

Colorectal cancer (CRC) is one of the most common malignancies worldwide and is associated with poor prognosis and high mortality. Despite advances in treatment with chemotherapy, CRC remains a major cause of drug resistance-related cancer deaths. One of the main reasons for such resistance is dysre...

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Veröffentlicht in:	Cancer letters 2021-02, Vol.498, p.31-41
Hauptverfasser:	Yu, Zhou, Du, Jiaying, Zhao, Yue, Gao, Yuan, Li, Yongxu, Zhao, Kai, Lu, Na
Format:	Artikel
Sprache:	eng
Schlagworte:	ABT-199 Animals Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Apoptosis Regulatory Proteins - metabolism Bridged Bicyclo Compounds, Heterocyclic - pharmacology Cancer Cancer therapies Cell Line Cell Line, Tumor Chemotherapy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - metabolism Cyclin-Dependent Kinase 9 - metabolism Cyclin-dependent kinases Design Down-Regulation - drug effects Drug resistance Enzyme inhibitors Flavonoids - pharmacology Flavopiridol Glycogen Synthase Kinase 3 beta - metabolism GSK-3β HCT116 Cells HEK293 Cells HT29 Cells Humans Immunoprecipitation Kinases Mcl-1 Mcl-1 protein Mice Mice, Inbred BALB C Mice, Nude Myeloid Cell Leukemia Sequence 1 Protein - metabolism Piperidines - pharmacology Plasmids Protein Kinase Inhibitors - pharmacology Proteins RNA polymerase Signal Transduction - drug effects Sulfonamides - pharmacology Synergism Toxicity Western blotting Xenografts
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