Molecular mechanism of genetic, epigenetic, and metabolic alteration in lung cancer

Medical Oncology, Год журнала: 2025, Номер 42(3)

Опубликована: Фев. 2, 2025

Язык: Английский

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Combining Network Pharmacology, Molecular Docking and Experimental Validation to Explore the Effects and Mechanisms of Indirubin on Acute Lymphoblastic Leukemia

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 1083 - 1103

Опубликована: Фев. 1, 2025

To investigate the effects and underlying mechanisms of indirubin in treating ALL using network pharmacology experimental validation. Potential targets indirubin- ALL-related genes were identified public databases. Core filtered through protein-protein interaction analysis Cytoscape. Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses conducted to explore potential against ALL. Drug-disease-functional annotation-signaling maps constructed. Molecular docking between core proteins was performed AutoDock Vina software. Finally, both vitro vivo experiments validate these findings. PPI eight ALL: AKT1, CASP3, mammalian target rapamycin. GO KEGG suggested that mechanism action involves multiple biological functions signaling pathways, with PI3K-AKT likely playing a central role. findings further confirmed strong binding affinity for targets. Both demonstrated inhibited cell proliferation induced cycle arrest apoptosis; may involve pathway. The pharmacology, as well validation elucidated, offering new insights therapeutic avenues treatment

Язык: Английский

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Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

MedComm, Год журнала: 2023, Номер 4(4)

Опубликована: Июль 10, 2023

Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant tumors. Neoadjuvant chemotherapy combined with limb-preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management OS. There been an urgent need identify new biomarkers develop specific targeted therapies. Recently, continued advancements genomic analysis have contributed identification clinically significant molecular diagnosing OS, acting as therapeutic targets, predicting prognosis. Additionally, contemporary classifications revealed that signaling pathways, including Wnt/β-catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD-1/PD-L1, MAPK, NF-κB, integral role onset, progression, metastasis, treatment response. These biological markers created avenues more accurate diagnosis relevant treatment. We herein present review recent findings modulatory pathways possible targets This also discusses current approaches, pathway-based therapies developed over past decade. covers involved curative effects traditional Chinese medicines context expression regulation genes proteins through inhibit cell growth. expected provide directions integrating genomic, molecular, profiles enhance

Язык: Английский

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Multiple forms of cell death: A focus on the PI3K/AKT pathway

Journal of Cellular Physiology, Год журнала: 2023, Номер 238(9), С. 2026 - 2038

Опубликована: Авг. 10, 2023

Abstract Cell death is a natural biological process that occurs in living organisms. Since 1963, extensive research has shed light on the occurrence, progress, and final outcome of cell death. According to different phenotypes, it classified into types, including apoptosis, pyroptosis, necroptosis, autophagy, ferroptosis, cuproptosis, so on. However, regardless form death, what we ultimately expect disappearance abnormal cells, such as tumor while normal cells survive. As result, vital investigate details triggers, potent regulators, executioners. Although significant progress been made understanding molecular pathways many aspects remain unclear because complex regulatory networks cells. Among them, phosphoinositide‐3‐kinase (PI3K)/protein kinase B(AKT) pathway discovered be crucial regulator process. AKT, proto‐oncogene, become major focus attention medical community due its role regulating multiplicity cellular functions counting metabolism, immunity, proliferation, survival, transcription, protein synthesis. Here, explored connection between PI3K/AKT aiming enhance our comprehension mechanism underlying this Such knowledge may pave way for subsequent development more effective disease treatments, finding suitable targets drug intervention.

Язык: Английский

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Targeting EGFR/PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma

Pharmaceutics, Год журнала: 2023, Номер 15(8), С. 2130 - 2130

Опубликована: Авг. 14, 2023

Hepatocellular carcinoma (HCC) poses a significant global health concern, with its incidence steadily increasing. The development of HCC is multifaceted, multi-step process involving alterations in various signaling cascades. In recent years, progress has been made understanding the molecular pathways that play central roles hepatocarcinogenesis. particular, EGFR/PI3K/AKT/mTOR pathway garnered renewed attention from both basic and clinical researchers. Preclinical studies vitro vivo have shown effectiveness targeting key components this human cells. Thus, these small molecule inhibitors holds promise as potential therapeutic option for patients HCC. review, we explore advancements role assess cascade strategy therapy based on preclinical studies.

Язык: Английский

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To Investigate the Occurrence and Development of Colorectal Cancer Based on the PI3K/AKT/mTOR Signaling Pathway

Frontiers in Bioscience-Landmark, Год журнала: 2023, Номер 28(2)

Опубликована: Фев. 24, 2023

Colorectal cancer (CRC) is the most common malignancy of gastrointestinal, however, underlying mechanisms CRC remain largely unknown. New evidence suggests that PI3K/AKT/mTOR pathway closely related to CRC. a classical signaling involved in variety biological processes, such as regulating cellular metabolism, autophagy, cell cycle progression, proliferation, apoptosis, and metastasis. Therefore, it plays crucial role occurrence development In this review, we focus on CRC, its application treatment We review importance tumorigenesis, proliferation pre-clinical clinical experience with several inhibitors

Язык: Английский

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Hepatocellular Carcinoma cells: activity of Amygdalin and Sorafenib in Targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death

BMC Complementary Medicine and Therapies, Год журнала: 2023, Номер 23(1)

Опубликована: Сен. 19, 2023

Sorafenib (Sor) is the only approved multikinase inhibitor indicated for treatment of HCC. Previous studies have shown that amygdalin (Amy) possesses anticancer activities against several cancer cell lines; we suggested these compounds might disrupt AMPK/mTOR and BCL-2. Therefore, current study used integrated in vitro silico approaches to figure out Amy Sor's possible synergistic activity targeting BCL-2 anti-angiogenesis apoptosis death HepG2 cells.Notably, demonstrated exceptional cytotoxic selectivity cells comparison normal WI-38 (IC50 = 5.21 mg/ml; 141.25 mg/ml), respectively. In contrast, were far more sensitive toxicity Sor. A substantial interaction between Sor was observed (CI50 0.56), which connected cycle arrest at S G2/M stages increased potential necroptosis. cotreatment resulted highest glutathione levels induction pro-autophagic genes AMPK, HGMB1, ATG5, Beclin 1, LC3, suppressed mTOR BCL2 anti-apoptotic gene. Finally, docking proposed binds active site AMPK enzyme, thus inhibiting its activity. This inhibition ultimately leads induces cells.Although vivo research using animal models needed confirm findings, our findings contribute evidence supporting Amy's effectiveness as an alternative therapeutic option

Язык: Английский

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Bufalin targeting BFAR inhibits the occurrence and metastasis of gastric cancer through PI3K/AKT/mTOR signal pathway

APOPTOSIS, Год журнала: 2023, Номер 28(9-10), С. 1390 - 1405

Опубликована: Май 30, 2023

Язык: Английский

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Beta-elemene: A phytochemical with promise as a drug candidate for tumor therapy and adjuvant tumor therapy

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 172, С. 116266 - 116266

Опубликована: Фев. 13, 2024

β-Elemene (IUPAC name: (1 S,2 S,4 R)-1-ethenyl-1-methyl-2,4-bis(prop-1-en-2-yl) cyclohexane), is a natural compound found in turmeric root. Studies have demonstrated its diverse biological functions, including anti-tumor properties, which been extensively investigated. However, these not yet reviewed. The aim of this review was to provide comprehensive summary β-elemene research, with respect disease treatment.

Язык: Английский

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Cell death pathways: molecular mechanisms and therapeutic targets for cancer

MedComm, Год журнала: 2024, Номер 5(9)

Опубликована: Сен. 1, 2024

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell can provide novel therapeutic strategies battling cancer. This review explores several key mechanisms apoptosis, necroptosis, autophagic death, ferroptosis, pyroptosis. The research gap addressed involves a thorough analysis how these be precisely targeted therapy, considering tumor heterogeneity adaptation. It delves into genetic epigenetic factors signaling cascades like phosphatidylinositol 3‐kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) mitogen‐activated protein kinase/extracellular signal‐regulated (MAPK/ERK) pathways, which are critical death. Additionally, interaction microenvironment with cells, particularly influence hypoxia, nutrient deprivation, immune cellular interactions, explored. Emphasizing strategies, this highlights emerging modulators inducers such as B lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, innovative approaches to induce ferroptosis provides insights therapy's future direction, focusing on multifaceted circumvent drug resistance. examination evolving underlines considerable clinical potential continuous necessity in‐depth exploration within scientific domain.

Язык: Английский

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