Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway

Journal of Experimental & Clinical Cancer Research : CR
Jian ZhouChunxue Bai

Abstract

Drug resistance is common in cancer chemotherapy. This study investigates the role of Glycerol kinase 5 (GK5) in mediating gefitinib resistance in NSCLC. The exosomal mRNA of GK5 was detected using a tethered cationic lipoplex nanoparticle (TCLN) biochip. Real-time PCR and Western blot were used to examine the expression of GK5 mRNA and protein in gefitinib-sensitive and -resistant human lung adenocarcinoma cells. The cell counting kit-8, EdU assay, flow cytometry, and JC-1 dye were used to measure cell proliferation, cell cycle, and the mitochondrial membrane potential. We found that the exosomal mRNA of GK5 in the plasma of patients with gefitinib-resistant adenocarcinoma was significantly higher compared with that of gefitinib-sensitive patients. The mRNA and protein levels of GK5 were significantly upregulated in gefitinib-resistant human lung adenocarcinoma PC9R and H1975 cells compared with gefitinib-sensitive PC9 cells. Silencing GK5 in PC9R cells induced mitochondrial damage, caspase activation, cell cycle arrest, and apoptosis via SREBP1/SCD1 signaling pathway. We demonstrated that GK5 confers gefitinib resistance in lung cancer by inhibiting apoptosis and cell cycle arrest. GK5 could be a novel therapeutic target for ...Continue Reading

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Citations

Jan 20, 2021·Clinical and Experimental Pharmacology & Physiology·Mengnan YanYao Shen
Jan 1, 2021·Environmental Pollution·Jiapeng JieDan Weng
May 29, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ya-Jia XieXing-Xing Fan

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Datasets Mentioned

BETA
AB032261.1

Methods Mentioned

BETA
Fluorescence
FACS
flow cytometry
xenograft
transfection

Software Mentioned

Rosetta
MATLAB
Image J

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis