Reversal of chemotherapy resistance in gastric cancer with traditional Chinese medicine as sensitizer: potential mechanism of action

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Фев. 20, 2025

Gastric cancer (GC) remains one of the most common types cancer, ranking fifth among cancer-related deaths worldwide. Chemotherapy is an effective treatment for advanced GC. However, development chemotherapy resistance, which involves malfunction several signaling pathways and consequence numerous variables interacting, seriously affects patient leads to poor clinical outcomes. Therefore, in order treat GC, it imperative find novel medications that will increase sensitivity reverse resistance. Traditional Chinese medicine (TCM) has been extensively researched as adjuvant medication recent years. It shown have anticancer benefits be crucial enhancing reducing Given this, mechanism resistance GC summed up this work. The theoretical foundation TCM a sensitizer established by introducing primary signal possible targets implicated improving reversing active ingredients.

Язык: Английский

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Exploring the Molecular Interactions Between Ferroptosis and the Wnt/β-Catenin Signaling Pathway: Implications for Cancer and Disease Therapy

Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104674 - 104674

Опубликована: Фев. 1, 2025

Язык: Английский

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Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis

Frontiers in Molecular Biosciences, Год журнала: 2025, Номер 12

Опубликована: Фев. 25, 2025

The incidence of Poorly cohesive carcinoma (PCC) has steadily risen in recent years, posing a significant clinical challenge. To reveal the anti-tumor effects Jianpi Yangzheng Xiaozheng granule (JPYZXZ) PCC, an initial investigation was performed using CCK-8, colony formation, scratch, and transwell assays. This followed by network pharmacology studies to gain deeper understanding JPYZXZ's impact on gastric cancer (GC). Then reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), glutathione (GSH), Oil Red O staining, BODIPY493/503, triglyceride (TG), cholesterol (TC) assay kits western blot (Wb) analysis were applied exam regulatory JPYZXZ ferroptosis lipid metabolism. Additionally, molecular docking Wb used further investigate mechanisms PCC. Finally, vivo animal conducted. results show that can inhibit proliferation migration PCC cell. It increases levels ROS, MDA, while declining content GSH, TC, TG, droplet accumulation within cellular compartments. indicates negatively regulate expression proteins, including peroxidase 4 (GPX4), cystine/glutamate antipoter SLC7A11 (xCT), fatty acid synthase (FASN), acetyl coenzyme A carboxylase 1 (ACC1). Furthermore, ferrostatin-1 (fer-1) is able reverse aforementioned markers Molecular analyses exhibits favorable binding affinity towards Stearoyl-Coenzyme desaturase (SCD1). Mechanism demonstrate capable down-regulating expressions proteins like SCD1, β-catenin, GPX4, xCT, which analogous SCD1 knockdown application inhibitor A939572. Nevertheless, when knocked down, unable downregulate these proteins. Animal have corroborated vitro tumor-inhibiting JPYZXZ. Therefore, this study offers first evidence inhibits progression orchestrating altering metabolism, mediated SCD1/Wnt/β-catenin pathway.

Язык: Английский

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Targeting FASN enhances cisplatin sensitivity via SLC7A11-mediated ferroptosis in cervical cancer

Translational Oncology, Год журнала: 2025, Номер 56, С. 102396 - 102396

Опубликована: Апрель 15, 2025

Язык: Английский

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Acute and subacute toxicity evaluation of ZhenzhuXiaoji decoction in preclinical models: implications for safe clinical use

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 15, 2025

Background ZhenzhuXiaoji Decoction (ZZXJD) is a traditional Chinese medicine formulation composed of five herbs: Ligustrum lucidum , Curcuma zedoaria Prunella vulgaris Hedyotis diffusa and Glycyrrhiza uralensis developed for the treatment hepatocellular carcinoma (HCC). Although early studies have demonstrated therapeutic potential ZZXJD, its safety profile, particularly regarding toxicity, remains underexplored. This study aims to evaluate both pharmacological effects toxicity ZZXJD in preclinical models determine clinical applicability. Study design Methods employed vitro vivo experiments assess ZZXJD. HHL-5 HEK-293 cell lines were treated with at varying concentrations (125, 250, 500, 1,000 μg/mL) 24, 48, 72 h on viability, apoptosis, necrosis. Acute subacute conducted male female mice, including assessments behavioral changes, body weight, organ liver/kidney functions. Additionally, routine blood tests performed identify immunostimulatory effects. Results In that inhibited proliferation cells dose-dependent manner induced apoptosis studies, mice low mid-dose groups exhibited no significant whereas high-dose group showed transient alterations liver kidney function markers, mice. These changes reversible following cessation. Blood indicated increased lymphocyte monocyte counts mice; however, these increases not statistically significant. Organ weight histopathological analyses revealed signs doses. Conclusion Treatment standard dosage did produce acute or toxic functions suggesting continued use cancer treatment. However, abnormalities markers observed higher Thus, regular monitoring recommended during use, especially when doses are employed.

Язык: Английский

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N6-methyladenosine (m6A) writer METTL5 represses the ferroptosis and antitumor immunity of gastric cancer

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Сен. 11, 2024

Язык: Английский

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Ferroptosis in Cancer: A new perspective on T cells

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113539 - 113539

Опубликована: Ноя. 1, 2024

Язык: Английский

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Molecular Mechanisms of Buzhong Yiqi Decoction in the Treatment of Gastric Cancer: A Network Pharmacology, Molecular Docking, and In Vitro Experimental Analysis

Peptide Science, Год журнала: 2024, Номер 116(6)

Опубликована: Июль 4, 2024

ABSTRACT Gastric cancer (GC) is the most common type of digestive system with high morbidity and mortality. Chemotherapy targeted therapy are used to treat patients advanced GC. However, side effects drug resistance two modalities remain main challenges. The Buzhong Yiqi decoction (BZYQD), a classical traditional Chinese medicine formula, has been reported for treatment various types cancers. underlying pharmacological mechanism not fully elucidated. Therefore, this study integrated network pharmacology, molecular docking, public databases, cell experiments explore potential bioactive compounds BZYQD's action against A total 245 targets BZYQD, 5291 GC‐related targets, 186 were identified as their through database. Network analysis confirmed AKT1, TP53, TNF, EGFR be core while observed quercetin, kaempferol, β‐Sitosterol. signaling pathways included PI3K‐AKT, MAPK, IL‐17. Molecular docking revealed good binding activity targets. Based on database's validation large number genes verified consistent study. Quercetin, β‐Sitosterol found significantly reduce growth GC cells in MTT experiment. current that BZYQD may inhibit progression by interfering such EGFR, MAPK3, regulating IL‐17 pathways.

Язык: Английский

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Unraveling the Ferroptosis-inducing Potential of Methanol Leaves Extract of Prosopis Juliflora Via Downregulation of SLC7A11 and GPX4 mRNA Expression in A549 Lung Cancer Cells

Current Medicinal Chemistry, Год журнала: 2024, Номер 32(7), С. 1442 - 1456

Опубликована: Окт. 25, 2024

Introduction: Prosopis juliflora has been employed in many traditional treatments. As evidenced by our earlier research, leaf methanol extract (PJME) a promising future the fight against lung cancer. It may also be used conjunction with other treatments to effectively manage Aims and Objective: The main objective of this study was explore potential PJME inhibit cancer A549 cells, along its underlying mechanisms action. Methods: antiproliferative effects were determined using MTT LDH tests. Apoptosis- inducing capacity evaluated DAPI staining, caspase-3 test, cytochrome C assay, PARP cleavage, qRT-PCR. To investigate mechanism action cancer, levels ROS, MMP, GSH, MDA, specific ferroptosis indicators measured. Results: experimental data current indicated that exposure cells reduced cell viability increased cellular cytotoxicity. apoptosis-inducing ability validated enhanced nuclear condensation, level caspase- 3, C, release. In addition, qRT-PCR investigations verified administration led decrease expression anti-apoptotic gene Bcl2 while enhancing mRNA pro-apoptotic genes, such as Bax caspase-3, cells. Conclusion: found activate pathways, elevated reactive oxygen species (ROS) generation, changes antioxidant markers (MDA GSH), decreased SLC7A11 GPX4. results present clearly showed inhibited proliferation induced reducing important targets Further research is necessary fully understand clinical efficacy before it can investigated supplemental or adjuvant therapy for

Язык: Английский

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Curcumol Enhances the Sensitivity of Gastric Cancer to Cisplatin Resistance by Inducing Ferroptosis Through the P62/KEAP1/NRF2 Pathway

Integrative Cancer Therapies, Год журнала: 2024, Номер 23

Опубликована: Янв. 1, 2024

Chemoresistance represented one of the challenges in treatment advanced gastric cancer (GC). Curcumol (CUR) was found to have a certain sensitizing effect on chemoresistance, although mechanism not yet fully understood.

Язык: Английский

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