FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385851206> ?p ?o ?g. }

• W4385851206 abstract "Non-small cell lung cancer (NSCLC) has a poor prognosis, and effective therapeutic strategies are lacking. The diabetes drug canagliflozin inhibits NSCLC cell proliferation and the mammalian target of rapamycin (mTOR) pathway, which mediates cell growth and survival, but it is unclear whether this drug can enhance response rates when combined with cytotoxic therapy. Here, we evaluated the effects of canagliflozin on human NSCLC response to cytotoxic therapy in tissue cultures and xenografts. Ribonucleic acid sequencing (RNA-seq), real-time quantitative PCR (RT-qPCR), metabolic function, small interfering ribonucleic acid (siRNA) knockdown, and protein expression assays were used in mechanistic analyses. We found that canagliflozin inhibited proliferation and clonogenic survival of NSCLC cells and augmented the efficacy of radiotherapy to mediate these effects and inhibit NSCLC xenograft growth. Canagliflozin treatment alone moderately inhibited mitochondrial oxidative phosphorylation and exhibited greater antiproliferative capacity than specific mitochondrial complex-I inhibitors. The treatment downregulated genes mediating hypoxia-inducible factor (HIF)-1α stability, metabolism and survival, activated adenosine monophosphate-activated protein kinase (AMPK) and inhibited mTOR, a critical activator of hypoxia-inducible factor-1α (HIF-1α) signaling. HIF-1α knockdown and stabilization experiments suggested that canagliflozin mediates antiproliferative effects, in part, through suppression of HIF-1α. Transcriptional regulatory network analysis pinpointed histone deacetylase 2 (HDAC2), a gene suppressed by canagliflozin, as a key mediator of canagliflozin's transcriptional reprogramming. HDAC2 knockdown eliminated HIF-1α levels and enhanced the antiproliferative effects of canagliflozin. HDAC2-regulated genes suppressed by canagliflozin are associated with poor prognosis in several clinical NSCLC datasets. In addition, we include evidence that canagliflozin also improves NSCLC response to chemotherapy. In summary, canagliflozin may be a promising therapy to develop in combination with cytotoxic therapy in NSCLC." @default.
• W4385851206 created "2023-08-17" @default.
• W4385851206 creator A5001013722 @default.
• W4385851206 creator A5003830194 @default.
• W4385851206 creator A5004596436 @default.
• W4385851206 creator A5009277937 @default.
• W4385851206 creator A5024749958 @default.
• W4385851206 creator A5031536033 @default.
• W4385851206 creator A5031924160 @default.
• W4385851206 creator A5032800128 @default.
• W4385851206 creator A5042906616 @default.
• W4385851206 creator A5043435077 @default.
• W4385851206 creator A5052061134 @default.
• W4385851206 creator A5056269283 @default.
• W4385851206 creator A5056355169 @default.
• W4385851206 creator A5057361837 @default.
• W4385851206 creator A5064403106 @default.
• W4385851206 creator A5065611718 @default.
• W4385851206 creator A5076165905 @default.
• W4385851206 creator A5087816082 @default.
• W4385851206 creator A5087859751 @default.
• W4385851206 date "2023-08-27" @default.
• W4385851206 modified "2023-10-12" @default.
• W4385851206 title "Canagliflozin mediates tumor suppression alone and in combination with radiotherapy in non‐small cell lung cancer (NSCLC) through inhibition of HIF‐1α" @default.
• W4385851206 cites W1539047554 @default.
• W4385851206 cites W1606165384 @default.
• W4385851206 cites W1883655199 @default.
• W4385851206 cites W1899125083 @default.
• W4385851206 cites W1974115114 @default.
• W4385851206 cites W1982219839 @default.
• W4385851206 cites W2016752484 @default.
• W4385851206 cites W2031954417 @default.
• W4385851206 cites W2036897871 @default.
• W4385851206 cites W2046187511 @default.
• W4385851206 cites W2066607735 @default.
• W4385851206 cites W2070910260 @default.
• W4385851206 cites W2071944097 @default.
• W4385851206 cites W2076908467 @default.
• W4385851206 cites W2081920342 @default.
• W4385851206 cites W2099013228 @default.
• W4385851206 cites W2102278945 @default.
• W4385851206 cites W2107277218 @default.
• W4385851206 cites W2111527534 @default.
• W4385851206 cites W2114969709 @default.
• W4385851206 cites W2126496132 @default.
• W4385851206 cites W2130410032 @default.
• W4385851206 cites W2139387872 @default.
• W4385851206 cites W2153949698 @default.
• W4385851206 cites W2154745425 @default.
• W4385851206 cites W2179438025 @default.
• W4385851206 cites W2467821377 @default.
• W4385851206 cites W2516478359 @default.
• W4385851206 cites W2587210786 @default.
• W4385851206 cites W2596281330 @default.
• W4385851206 cites W2773564421 @default.
• W4385851206 cites W2788841106 @default.
• W4385851206 cites W2806368379 @default.
• W4385851206 cites W2917207851 @default.
• W4385851206 cites W2923057410 @default.
• W4385851206 cites W2939222610 @default.
• W4385851206 cites W2947112537 @default.
• W4385851206 cites W2982277050 @default.
• W4385851206 cites W2982872965 @default.
• W4385851206 cites W2995072671 @default.
• W4385851206 cites W2995298233 @default.
• W4385851206 cites W3004897542 @default.
• W4385851206 cites W3005537185 @default.
• W4385851206 cites W3011286029 @default.
• W4385851206 cites W3015450697 @default.
• W4385851206 cites W3091049124 @default.
• W4385851206 cites W3094518505 @default.
• W4385851206 cites W3128646645 @default.
• W4385851206 cites W3129927700 @default.
• W4385851206 cites W3142978815 @default.
• W4385851206 cites W3178844073 @default.
• W4385851206 cites W3208716233 @default.
• W4385851206 cites W4200199725 @default.
• W4385851206 cites W4206907302 @default.
• W4385851206 cites W4211075515 @default.
• W4385851206 cites W4226175083 @default.
• W4385851206 cites W4230985598 @default.
• W4385851206 cites W4234236664 @default.
• W4385851206 cites W4293653706 @default.
• W4385851206 cites W4309026454 @default.
• W4385851206 cites W4317500708 @default.
• W4385851206 cites W4318542616 @default.
• W4385851206 doi "https://doi.org/10.1002/1878-0261.13508" @default.
• W4385851206 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37584455" @default.
• W4385851206 hasPublicationYear "2023" @default.
• W4385851206 type Work @default.
• W4385851206 citedByCount "0" @default.
• W4385851206 crossrefType "journal-article" @default.
• W4385851206 hasAuthorship W4385851206A5001013722 @default.
• W4385851206 hasAuthorship W4385851206A5003830194 @default.
• W4385851206 hasAuthorship W4385851206A5004596436 @default.
• W4385851206 hasAuthorship W4385851206A5009277937 @default.
• W4385851206 hasAuthorship W4385851206A5024749958 @default.
• W4385851206 hasAuthorship W4385851206A5031536033 @default.
• W4385851206 hasAuthorship W4385851206A5031924160 @default.
• W4385851206 hasAuthorship W4385851206A5032800128 @default.

• next