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Objective: To investigate the effect of expression on the proliferation and the accumulation of intracellular drug of HL60/A and HL60 cells and its possible molecular mechanism.
Methods: Lentiviral transfection technology was used to construct HL60/A and HL60 cells with knocked down or overexpressed and their control cells. The efficiency of knockdown and overexpression was evaluated by Western blot. The cell proliferation was detected by CCK-8 assay. The intracellular drug accumulation was detected by laser confocal detection and flow cytometry. The expression levels of MRP1, P-gP and p-AKT were evaluated by flow cytometry and Western blot.
Results: After was knocked down,the proliferation ability of HL60/A cells was significantly reduced, the accumulation of intracellular drug was significantly increased and the expression of MRP1 and P-gP protein were decreased. After was overexpressed, the proliferation ability of HL60 was significantly increased, the accumulation of intracellular drug was significantly decreased and the expression of MRP1 and P-gP protein were increased. Intervention of LY294002 significantly antagonized the promotion on cell proliferation, the inhibition on intracellular drug accumulation and the expression of MRP1 and P-gP mediated by overexpressing in HL60 cells.
Conclusion: can promote cell proliferation, improve the expression of MRP1 and P-gP by activating PI3K/AKT signal, and reduce intracellular drug accumulation.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2024.01.012 | DOI Listing |
Mol Biol Rep
September 2025
School of Pharmacy, Heilongjiang University of Chinese Medicine, NO 24 Heping Road, 150040, Harbin, P. R. China.
Lysosome-dependent cell death (LDCD) is a regulated form of cell death initiated by increased lysosomal membrane permeability, leading to the cytoplasmic release of lysosomal enzymes and subsequent cellular damage. Molecular mechanisms controlling LDCD include lysosomal membrane instability and lysosomal enzyme release, which together lead to cell damage. A more profound comprehension of these underlying mechanisms may reveal new therapeutic targets for diseases associated with lysosomal dysfunction.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
September 2025
Certara UK Ltd., Level 2 Acero, 1 Concourse Way, Sheffield, UK.
Therapeutic oligonucleotides (TOs) represent an emerging modality, which offers a promising alternative treatment option, particularly for intracellular targets. The two types of TOs, antisense oligonucleotides (ASO) and small interfering RNAs (siRNAs), distribute highly into tissues, especially into the liver and the kidneys. However, molecular processes at the cellular level such as the uptake into the cell, endosomal escape, binding to the target mRNA, and redistribution back to the systemic circulation are not well characterized because experimental data and assays are lacking.
View Article and Find Full Text PDFInt J Nanomedicine
September 2025
The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People's Republic of China.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease, the incidence of which continues to rise globally, and existing therapeutic options are limited by low drug bioavailability and systemic side effects. In this study, we systematically investigated the challenges of the special gastrointestinal environment of UC patients for oral drug delivery, such as extreme pH, degradation by digestive enzymes, metabolism of intestinal flora and obstruction of the intestinal mucosal barrier, and summarized the potential of plant-derived Exosome-like Nanovesicles (PELNs) as a novel delivery system. PELNs are produced by plant cells and mainly consist of proteins, RNA, lipids and plant active molecules.
View Article and Find Full Text PDFMater Today Bio
October 2025
School of Pharmacy, Henan Medical University, Xinxiang, Henan, China.
Breast cancer continues to present a major clinical hurdle, largely attributable to its aggressive metastatic behavior and the suboptimal efficacy of standard chemotherapeutic regimens. Cisplatin (CDDP) is a representative platinum drug in the treatment of breast cancer, however, its therapeutic application is often constrained by systemic toxicity and the frequent onset of chemoresistance. Here, we introduce a novel charge-adaptive nanoprodrug system, referred to as PP@, engineered to respond to tumor-specific conditions.
View Article and Find Full Text PDFAm J Psychiatry
September 2025
School of Psychology, Faculty of Science, University of Sydney, and Australia Brain and Mind Centre, University of Sydney, Sydney, Australia.
Objective: The objective of this study was to comprehensively examine the real-world safety of esketamine using 58 months of postapproval data in the United States.
Methods: U.S.