GANT61 surmounts drug resistance of ADR by upregulating lysosome activities and reducing BCL2 expression in HL-60/ADR cells DOI Creative Commons
Cheng Zhou, Liang Zhao, Ming Zhou

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Dec. 26, 2024

Drug resistance remains a significant obstacle to Acute myeloid leukemia (AML) successful treatment, often leading therapeutic failure. Our previous studies demonstrated that Glioma-associated oncogene-1 (GLI1) reduces chemotherapy sensitivity and promotes cell proliferation in AML cells. GANT61, an inhibitor of GLI1, emerges as promising candidate treatment. This study aims explore the effects combination GANT61 Adriamycin (ADR) on cells elucidate mechanisms through which may potentiate ADR. lines primary were studied evaluate GANT61. Flow cytometry assays used verify apoptosis. Cell Counting Kit-8 (CCK-8) EDU+ staining observe changes viability cytotoxic effect different drugs. The transcriptomic profiles HL-60/ADR with or without treatment compared via RNA-Seq analysis. Kyoto Encyclopedia Genes Genomes (KEGG) analyses Gene Set Enrichment Analysis (GSEA) performed for differentially expressed genes (DEGs) reveal underlying BCL2, Bax protein mRNA expression levels assessed by Western blot Real-time polymerase chain reaction (RT-PCR). found ADR synergistically inhibits while enhancing apoptosis cells, does not significantly exacerbate myelosuppression. Mechanistically, GSEA revealed enrichment gene set associated KEGG term "Apoptosis" "Lysosome" treated Meanwhile, was identified third most relevant pathway enriched lysosomal DEGs, BCL2 showed negative correlation these DEGs patients. RT-PCR analysis disclosed restrained Lastly, we proved venetoclax, inhibitor, co-treatment improved effectively reversed upregulating lysosome activities downgrading expression, providing new strategy acceptable toxicity AML-resistant

Language: Английский

Advances in artificial intelligence-envisioned technologies for protein and nucleic acid research DOI Creative Commons
Amol D. Gholap, Abdelwahab Omri

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104362 - 104362

Published: April 1, 2025

Artificial intelligence (AI) and machine learning (ML) have revolutionized pharmaceutical research, particularly in protein nucleic acid studies. This review summarizes the current status of AI ML applications sector, focusing on innovative tools, web servers, databases. paper highlights how these technologies address key challenges drug development including high costs, lengthy timelines, complexity biological systems. Furthermore, potential personalized medicine, cancer response prediction, biomarker identification is discussed. The integration research promises to accelerate discovery, reduce ultimately lead more effective therapeutic strategies.

Language: Английский

Citations

0
GANT61 surmounts drug resistance of ADR by upregulating lysosome activities and reducing BCL2 expression in HL-60/ADR cells DOI Creative Commons
Cheng Zhou, Liang Zhao, Ming Zhou

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Dec. 26, 2024

Drug resistance remains a significant obstacle to Acute myeloid leukemia (AML) successful treatment, often leading therapeutic failure. Our previous studies demonstrated that Glioma-associated oncogene-1 (GLI1) reduces chemotherapy sensitivity and promotes cell proliferation in AML cells. GANT61, an inhibitor of GLI1, emerges as promising candidate treatment. This study aims explore the effects combination GANT61 Adriamycin (ADR) on cells elucidate mechanisms through which may potentiate ADR. lines primary were studied evaluate GANT61. Flow cytometry assays used verify apoptosis. Cell Counting Kit-8 (CCK-8) EDU+ staining observe changes viability cytotoxic effect different drugs. The transcriptomic profiles HL-60/ADR with or without treatment compared via RNA-Seq analysis. Kyoto Encyclopedia Genes Genomes (KEGG) analyses Gene Set Enrichment Analysis (GSEA) performed for differentially expressed genes (DEGs) reveal underlying BCL2, Bax protein mRNA expression levels assessed by Western blot Real-time polymerase chain reaction (RT-PCR). found ADR synergistically inhibits while enhancing apoptosis cells, does not significantly exacerbate myelosuppression. Mechanistically, GSEA revealed enrichment gene set associated KEGG term "Apoptosis" "Lysosome" treated Meanwhile, was identified third most relevant pathway enriched lysosomal DEGs, BCL2 showed negative correlation these DEGs patients. RT-PCR analysis disclosed restrained Lastly, we proved venetoclax, inhibitor, co-treatment improved effectively reversed upregulating lysosome activities downgrading expression, providing new strategy acceptable toxicity AML-resistant

Language: Английский

Citations

0