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Series GSE239688 Query DataSets for GSE239688
Status Public on Sep 10, 2023
Title The SGLT2 inhibitor canagliflozin suppresses growth and enhances prostate cancer response to radiotherapy
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Radiotherapy (RT) is a non-invasive standard treatment for prostate cancer (PC). However, PC develops radio-resistance, highlighting a need for agents to improve RT response. Canagliflozin, an inhibitor of sodium-glucose co-transporter-2, is approved for use in diabetes and heart failure, but is also shown to inhibit PC growth. However, whether canagliflozin can improve RT response in PC remains unknown. Here, we show that well-tolerated doses of canagliflozin suppress proliferation and survival of androgen-sensitive and insensitive human PC cells and tumors and sensitize them to RT. Canagliflozin blocks mitochondrial respiration, promotes AMPK activity, inhibits the MAPK and mTOR-p70S6k/4EBP1 pathways, activates cell cycle checkpoints, and inhibits proliferation in part through HIF-1š›¼ suppression. Canagliflozin mediates transcriptional reprogramming of several metabolic and survival pathways known to be regulated by ETS and E2F family transcription factors. Genes downregulated by canagliflozin are associated with poor PC prognosis. This study lays the groundwork for clinical investigation of canagliflozin in PC prevention and treatment in combination with RT.
Overall design In this study, RNAseq was designed to examined canagliflozinā€™s anti-tumor mechanism of action alone and in combination with radiotherapy in CRPC and mCRPC models of prostate cancer.
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Contributor(s) Ali A, Mekhaeil B, Biziotis O, Tsakiridis EE, Ahmadi E, Wu J, Wang S, Singh K, Menjolian G, Farrell T, Mesci A, Liu S, Berg T, Bramson JL, Steinberg GR, Tsakiridis T
Citation(s) 37684337
Submission date Jul 31, 2023
Last update date Sep 10, 2023
Contact name Amr Mohamed Ahmed Ali
Phone 7055077573
Organization name Mcmaster University
Department Oncology
Lab Dr. Tsakiridis
Street address 699 concession street-4-212
City Hamilton
State/province ON
ZIP/Postal code L8V2C5
Country Canada
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (18)
GSM7670010 PC3 cells treated with DMSO (Control A) 24Hr
GSM7670011 PC3 cells treated with DMSO (Control B) 24Hr
GSM7670012 PC3 cells treated with DMSO (Control C) 24Hr
BioProject PRJNA1000568

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Supplementary file Size Download File type/resource
GSE239688_1-_22RV1_rlog_normalized_feature_count_RNAseq_List_Canagliflozin_10uM_vs_Control_.xlsx 3.3 Mb (ftp)(http) XLSX
GSE239688_2-_22RV1_rlog_FDR_filter_normalized_feature_count_RNAseq_List_Radiation_5Gy_vs_Control_.xlsx 1.7 Mb (ftp)(http) XLSX
GSE239688_3-_22RV1_rlog_normalized_feature_count_RNAseq_List_Combination_canagliflozin_10um+radiation_5gy_vs_Control_.xlsx 4.3 Mb (ftp)(http) XLSX
GSE239688_4-_22RV1_rlog_normalized_feature_count_RNAseq_List_Irradiated_22RV1_5Gy_vs_irradiated_22RV1_5Gy_treated_with_canagliflozin_10uM_.xlsx 4.4 Mb (ftp)(http) XLSX
GSE239688_PC3_normalized_feature_count_RNAseq_List_Canagliflozin_10uM_vs_Control_.xlsx 3.1 Mb (ftp)(http) XLSX
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