ATP-binding cassette efflux transporters and MDR in cancer

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(5), P. 103537 - 103537

Published: Feb. 16, 2023

Language: Английский

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A bioinformatics analysis, pre-clinical and clinical conception of autophagy in pancreatic cancer: Complexity and simplicity in crosstalk

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106822 - 106822

Published: June 17, 2023

Pancreatic cancer (PC) is a serious gastrointestinal tract disease for which the 5-year survival rate less than 10%, even in developed countries such as USA. The genomic profile alterations and dysregulated biological mechanisms commonly occur PC. Macroautophagy/autophagy cell death process that maintained at basal level physiological conditions, whereas its often changes during tumorigenesis. function of autophagy human cancers dual can be oncogenic onco-suppressor. Autophagy potent controller tumorigenesis supportive PC escalates growth cells suppression mediate death. also determines metastasis cells, it control EMT affecting migration. Moreover, starvation hypoxia stimulate glycolysis, glycolysis induction mediated by enhancing Furthermore, protective stimulates drug resistance gemcitabine inhibition enhance radiosensitivity. degrade MHC-I to immune evasion regulates polarization macrophages tumor microenvironment. Modulation activity provided silibinin, ursolic acid, chrysin huaier treatment Non-coding RNAs are controllers improve therapy response patients. mitophagy shows dysregulation PC, proliferation cells. Therefore, bioinformatics analysis demonstrates autophagy-related proteins genes biomarkers.

Language: Английский

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Dysregulated Signalling Pathways Driving Anticancer Drug Resistance

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12222 - 12222

Published: July 30, 2023

One of the leading causes death worldwide, in both men and women, is cancer. Despite significant development therapeutic strategies, inevitable emergence drug resistance limits success impedes curative outcome. Intrinsic acquired are common mechanisms responsible for cancer relapse. Several factors crucially regulate tumourigenesis resistance, including physical barriers, tumour microenvironment (TME), heterogeneity, genetic epigenetic alterations, immune system, burden, growth kinetics undruggable targets. Moreover, transforming factor-beta (TGF-β), Notch, epidermal factor receptor (EGFR), integrin-extracellular matrix (ECM), nuclear kappa-light-chain-enhancer activated B cells (NF-κB), phosphoinositol-3-kinase/protein kinase B/mammalian target rapamycin (PI3K/Akt/mTOR), wingless-related integration site (Wnt/β-catenin), Janus kinase/signal transducers activators transcription (JAK/STAT) RAS/RAF/mitogen-activated protein (MAPK) signalling pathways some key players that have a pivotal role mechanisms. To guide future treatments improve results, deeper comprehension necessary. This review covers intrinsic gives comprehensive overview recent research on enable to bypass barriers put up by treatments, and, like “satellite navigation”, find alternative routes which carry their “journey” progression.

Language: Английский

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Cell membrane-camouflaged bufalin targets NOD2 and overcomes multidrug resistance in pancreatic cancer

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 71, P. 101005 - 101005

Published: Aug. 21, 2023

Multidrug resistance in pancreatic cancer poses a significant challenge clinical treatment. Bufalin (BA), compound found secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its application. Hence, present study aimed to develop cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) assess potential counter chemoresistance cancer.The toxicity CBAP was evaluated by electrocardiogram, body weight, distress score, nesting behavior mice. In addition, anticarcinoma activity underlying mechanism were investigated both vitro vivo.CBAP significantly mitigated BA-mediated acute enhanced sensitivity several drugs, such as gemcitabine, 5-fluorouracil, FOLFIRINOX. Mechanistically, directly bound nucleotide-binding oligomerization domain containing protein 2 (NOD2) inhibited expression nuclear factor kappa-light-chain-enhancer activated B cells. This inhibits ATP-binding cassette transporters, which are responsible for cells.Our findings indicate that NOD2. Combining with standard-of-care chemotherapeutics represents safe efficient strategy treatment cancer.

Language: Английский

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m6A eraser FTO impairs gemcitabine resistance in pancreatic cancer through influencing NEDD4 mRNA stability by regulating the PTEN/PI3K/AKT pathway

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Aug. 22, 2023

Gemcitabine resistance has brought great challenges to the treatment of pancreatic cancer. The N6-methyladenosine (m6A) mutation been shown have a significant regulatory role in chemosensitivity; however, it is not apparent whether gemcitabine can be regulated by fat mass and obesity-associated protein (FTO).Cells with established tissues from cancer patients were used evaluate FTO expression. biological mechanisms effects on resistant cells investigated using CCK-8, colony formation assay, flow cytometry, inhibitory concentration 50. Immunoprecipitation/mass spectrometry, MeRIP-seq, RNA sequencing RIP assays, stability, luciferase reporter, pull down assays employed examine mechanism affecting cells.The results revealed that was substantially expressed gemcitabine. Functionally, could enhanced FTO, while its depletion inhibited growth tumor vivo. spectrometry showed bound USP7 deubiquitinated USP7, leading upregulation FTO. At same time, knockdown significantly decreased expression level NEDD4 an m6A-dependent manner. immunoprecipitation verified YTHDF2 as reader NEDD4, which promoted chemoresistance cells. markedly increased PTEN NEDD4-dependent manner influenced chemosensitivity through PI3K/AKT pathway cells.In conclusion, we found demethylates manner, then influences thereby affects pathway. We also identified upregulated USP7.

Language: Английский

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Emerging Targets in Amyotrophic lateral sclerosis (ALS): The Promise of ATP-Binding Cassette (ABC) transporter Modulation

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: 476, P. 115242 - 115242

Published: Sept. 6, 2024

Language: Английский

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Ginkgetin improved experimental colitis by inhibiting intestinal epithelial cell apoptosis through EGFR/PI3K/AKT signaling

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(14)

Published: July 14, 2024

Abstract Excessive apoptosis of intestinal epithelial cells leads to barrier dysfunction, which is not only one the pathological features inflammatory bowel disease (IBD) but also a therapeutic target. A natural plant extract, Ginkgetin (GK), has been reported have anti‐apoptotic activity, its role in IBD unknown. This study aimed explore whether GK anti‐colitis effects and related mechanisms. An experimental colitis model induced by dextran sulfate sodium (DSS) was established, found relieve DSS‐induced mice as evidenced improvements weight loss, colon shortening, Disease Activity Index (DAI), macroscopic tissue scores, proinflammatory mediators. In addition, DSS TNF‐α‐induced colonic organoids, protected inhibited cell apoptosis, improving permeability inhibiting number apoptotic expression key regulators (cleaved caspase 3, Bax Bcl‐2). The underlying mechanism GK's protective effect explored bioinformatics, rescue experiments molecular docking, it that might directly target activate EGFR, thereby interfering with PI3K/AKT signaling inhibit vivo vitro. conclusion, colitis, at least part, activating EGFR activation, explaining for ameliorating may provide new options treatment IBD.

Language: Английский

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miR‐135b‐5p/PDE3B Axis Regulates Gemcitabine Resistance in Pancreatic Cancer Through Epithelial‐Mesenchymal Transition

Molecular Carcinogenesis, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Gemcitabine-based chemotherapy is an effective treatment for pancreatic cancer (PC), but gemcitabine resistance frequently compromises the therapeutic efficacy, resulting in clinical chemotherapeutic failure and a poor prognosis patients. In this study, we investigated mechanisms of chemoresistance PC by examining roles microRNAs linked to their downstream signaling pathways. vitro experiments were performed alter miR-135b-5p levels parental drug-resistant cells probe its function. targets PDE3B was confirmed using RNA-seq technology screen gemcitabine-resistance-associated mRNAs PC. A series rescue after cotransfection, demonstrating that could reverse miR-135b-5p-mediated epithelial-mesenchymal transition (EMT). These findings indicate miR-135b-5p/PDE3B axis generates stimulating EMT pathway, which provides new insights into

Language: Английский

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Expression of Chemoresistance-Associated ABC Proteins in Hepatobiliary, Pancreatic and Gastrointestinal Cancers

Cancers, Journal Year: 2022, Volume and Issue: 14(14), P. 3524 - 3524

Published: July 20, 2022

Hepatobiliary, pancreatic, and gastrointestinal cancers account for 36% of the ten million deaths caused by cancer worldwide every year. The two main reasons this high mortality are their late diagnosis refractoriness to pharmacological treatments, regardless whether these based on classical chemotherapeutic agents, targeted drugs, or newer immunomodulators. Mechanisms chemoresistance (MOC) defining multidrug resistance (MDR) phenotype each tumor depend synergic function proteins encoded more than one hundred genes classified into seven groups (MOC1-7). Among them, efflux active agents from cells across plasma membrane members superfamily ATP-binding cassette (ABC) (MOC-1b) plays a crucial role in determining MDR. Although families human ABC known, only few pumps (mainly MDR1, MRP1-6, BCRP) have been associated with reducing drug content hence inducing hepatobiliary, cells. present descriptive review, which compiles updated information expression proteins, will be helpful because there is still some confusion actual relevance response regimens currently used treating cancers. Moreover, we aim define MOC pattern tumor-by-tumor basis, even dynamic way, it can vary during progression chemotherapy. This indispensable developing novel strategies sensitization.

Language: Английский

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Revving the engine: PKB/AKT as a key regulator of cellular glucose metabolism

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Glucose metabolism is of critical importance for cell growth and proliferation, the disorders which have been widely implicated in cancer progression. uptake achieved differently by normal cells cells. Even an aerobic environment, tend to undergo through glycolysis rather than oxidative phosphorylation pathway. Disordered metabolic syndrome characterized elevated levels metabolites that can cause changes tumor microenvironment, thereby promoting recurrence metastasis. The activation glycolysis-related proteins transcription factors involved regulation cellular glucose metabolism. Changes activity are closely related protein kinase B (PKB/AKT). This review discusses recent findings on AKT tumors. Furthermore, summarizes potential each process throughout provide a theoretical basis as target cancers.

Language: Английский

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