Mechanism of sorafenib resistance associated with ferroptosis in HCC

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Июнь 7, 2023

Hepatocellular carcinoma (HCC) is the most familiar primary hepatic malignancy with a poor prognosis. The incidence of HCC and associated deaths have risen in recent decades. Sorafenib first drug to be approved by Food Drug Administration (FDA) for routine use first-line therapy patients advanced HCC. However, only about 30% will benefited from sorafenib therapy, resistance typically develops within 6 months. In years, mechanisms gained attention growing number researchers. A promising field current studies ferroptosis, which novel form cell death differing apoptosis, necroptosis, autophagy. This process dependent on accumulation intracellular iron reactive oxygen species (ROS). Furthermore, increase levels ROS can significantly observed cells resistant sorafenib. article reviews that are related evaluates relationship between ferroptosis resistance, explores new therapeutic approaches capable reversing through modulation ferroptosis.

Язык: Английский

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Machine learning and molecular subtyping reveal the impact of diverse patterns of cell death on the prognosis and treatment of hepatocellular carcinoma

Computational Biology and Chemistry, Год журнала: 2025, Номер 115, С. 108360 - 108360

Опубликована: Янв. 27, 2025

Язык: Английский

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ESR1-dependent suppression of LCN2 transcription reverses autophagy-linked ferroptosis and enhances sorafenib sensitivity in hepatocellular carcinoma

Journal of Physiology and Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Язык: Английский

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Upregulation of CSNK1A1 induced by ITGB5 confers to hepatocellular carcinoma resistance to sorafenib in vivo by disrupting the EPS15/EGFR complex

Pharmacological Research, Год журнала: 2023, Номер 192, С. 106789 - 106789

Опубликована: Май 4, 2023

Oral multitarget tyrosine kinase inhibitors (TKIs), such as sorafenib, which suppress tumor cell proliferation and angiogenesis, have been approved to treat patients with hepatocellular carcinoma (HCC). Of note, only approximately 30% of can benefit from TKIs, this population usually acquires drug resistance within 6 months. In study, we intended explore the mechanism associated regulating sensitivity HCC TKIs. We revealed that integrin subunit β 5 (ITGB5) is abnormally expressed in contributes decreased sorafenib. Mechanistically, unbiased mass spectrometry analysis using ITGB5 antibodies interacts EPS15 prevent degradation EGFR cells, activates AKT-mTOR signaling MAPK pathway reduce cells addition, showed CSNK1A1 binds cells. Further study indicated increased protein level through EGFR-AKT-mTOR HCC. Upregulated phosphorylates enhance interaction between activate Thus, identified a positive feedback loop ITGB5-EPS15-EGFR-CSNK1A1 This finding provides theoretical basis for future development therapeutic strategies improve anti-HCC efficacy

Язык: Английский

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Role of exosomes in hepatocellular carcinoma and the regulation of traditional Chinese medicine

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Янв. 17, 2023

Hepatocellular carcinoma (HCC) usually occurs on the basis of chronic liver inflammatory diseases and cirrhosis. The microenvironment plays a vital role in tumor initiation progression. Exosomes, which are nanometer-sized membrane vesicles secreted by number cell types. Exosomes carry multiple proteins, DNAs various forms RNA, mediators cell-cell communication regulate microenvironment. In recent decade, many studies have demonstrated that exosomes involved between HCC cells stromal cells, including endothelial macrophages, hepatic stellate immune serve as regulator proliferation metastasis, evasion immunotherapy. addition, can also be used for diagnosis treatment HCC. They potentially specific biomarkers early drug delivery vehicles Chinese herbal medicine, is widely prevention China, may release exosomes-mediated intercellular communication. this review, we summarized latest progresses initiation, progression potential value Traditional medicine biological behaviors

Язык: Английский

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Long-term di-(2-ethylhexyl) phthalate exposure reduces sorafenib treatment efficacy by enhancing mesenchymal transition in hepatocellular carcinoma

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 273, С. 116161 - 116161

Опубликована: Март 1, 2024

Di(2-ethylhexyl) phthalate (DEHP) is a worldwide common plasticizer. Nevertheless, DEHP easily leached out to the environment due lack of covalent bonds with plastic. High dose exposure often observed in hemodialysis patients because continual usage plastic medical devices. Although liver major organ that catabolizes DEHP, impact long-term on sensitivity cancer chemotherapy remains unclear. In this study, we established DEHP-exposed hepatocellular carcinoma (HCC) cells and two NOD/SCID mice models investigate effects underlying mechanisms chemosensitivity HCC. The results showed potentially increased epithelial-mesenchymal transition (EMT) HCC cells. Next generation sequencing cell adhesion/migratory related genes expression blunted sorafenib treatment induced alterations. Long-term reduced sorafenib-induced anti-migratory effect by enhancing EMT transcription factors (slug, twist, ZEB1) mesenchymal protein (vimentin) expression. model, exhibited higher growth rate. Regarding anti-HCC sorafenib, subcutaneous HuH7 tumor grew slowly sorafenib-treated mice. Nonetheless, anti-tumor was not Higher markers proliferating nuclear antigen (PCNA) were found conclusion, promoted migratory activity decreased tumor-bearing

Язык: Английский

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Making Sense of Antisense lncRNAs in Hepatocellular Carcinoma

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(10), С. 8886 - 8886

Опубликована: Май 17, 2023

Transcriptome complexity is emerging as an unprecedented and fascinating domain, especially by high-throughput sequencing technologies that have unveiled a plethora of new non-coding RNA biotypes. This review covers antisense long RNAs, i.e., lncRNAs transcribed from the opposite strand other known genes, their role in hepatocellular carcinoma (HCC). Several sense-antisense transcript pairs been recently annotated, mammalian genomes, understanding evolutionary sense functional for human health diseases only beginning. Antisense dysregulation significantly involved hepatocarcinogenesis, where they can act oncogenes or oncosuppressors, thus playing key tumor onset, progression, chemoradiotherapy response, deduced many studies discussed here. Mechanistically, regulate gene expression exploiting various molecular mechanisms shared with ncRNA molecules, exploit special on corresponding due to sequence complementarity, exerting epigenetic, transcriptional, post-transcriptional, translational controls. The next challenges will be piecing together complex regulatory networks driven and, ultimately, assigning them function physiological pathological contexts, addition defining prospective novel therapeutic targets innovative diagnostic tools.

Язык: Английский

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Tumor microenvironment responsive nano-platform for overcoming sorafenib resistance of hepatocellular carcinoma

Materials Today Bio, Год журнала: 2023, Номер 24, С. 100902 - 100902

Опубликована: Дек. 15, 2023

Hepatocellular carcinoma (HCC) is a malignant tumor, which seriously jeopardizes human health. The 5-year relative survival rate of HCC only about 18%. Sorafenib, small molecule multi-targeted tyrosine kinase inhibitor (MTKI), has been classified as the first-line treatment scheme for and significantly extended median time patients with advanced HCC. Nevertheless, emergence sorafenib resistance substantially hampered its further clinical application. Herein, nano-platform based on phototherapy molecular targeted therapy (SMTT) was devised to overcome reduce adverse effects. Hollow mesoporous manganese dioxide (H–MnO2) prepared by hard template method, H–MnO2 used load Chlorin e6 (Ce6). Subsequently, nanoparticle (NPs) were modified dopamine optimize biocompatibility. final NPs (MCS NPs) exhibit regular spherical shape hydrated particle size approximately 97.02 nm. MCS can not possess tumor microenvironment (TME) stimuli-responsive drug release performance but also enhance efficacy photodynamic reverse alleviating hypoxia. Under action (Ce6) combined (sorafenib), manifest satisfactory antitumor effect sorafenib-sensitive or sorafenib-resistant cells, retain antiangiogenic properties sorafenib. In nude mouse subcutaneous model constructed demonstrated superior imaging ability excellent inhibition group without laser irradiation 53.4 %, while high 100 %. novel smart TME-responsive shows great potential overcoming realizes multimodality

Язык: Английский

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TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP pathway

Cancer Science, Год журнала: 2024, Номер 115(5), С. 1476 - 1491

Опубликована: Март 12, 2024

Abstract Liver cancer is the sixth most common and third leading cause of cancer‐related death globally. Despite efforts being made in last two decades diagnosis treatment, 5‐year survival rate liver remains extremely low. TRIM21 participates metabolism, glycolysis, immunity, chemosensitivity metastasis by targeting various substrates for ubiquitination. serves as a prognosis marker human hepatocellular carcinoma (HCC), but mechanism which regulates HCC tumorigenesis progression elusive. In this study, we demonstrated that protein levels were elevated HCC. Elevated expression was associated with poor survival. Knockdown cell lines significantly impaired growth enhanced sorafenib‐induced toxicity. Mechanistically, found knockdown resulted cytosolic translocation inactivation YAP. At molecular level, further identified interacted induced ubiquitination MST1, MST1 degradation YAP activation. or overexpression reversed knockdown‐induced impairment chemosensitivity. Taken together, current study demonstrates novel Hippo pathway reveals TRM21 critical factor promotes chemoresistance

Язык: Английский

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Ropivacaine synergizes with sorafenib to induce apoptosis of hepatocellular carcinoma cells via the IL‐6/STAT3 pathway

Cancer Science, Год журнала: 2024, Номер 115(9), С. 2923 - 2930

Опубликована: Июль 16, 2024

Abstract The development of resistance in hepatocellular carcinoma (HCC) cells limits the effectiveness sorafenib, but combination therapy with other drugs may have a positive effect. However, effect ropivacaine combined sorafenib on treatment HCC and its potential regulatory mechanisms remain unclear. proliferation apoptosis treated ropivacaine, plus were analyzed by cell‐counting kit 8 flow cytometry. protein levels measured Western blot. antitumor their was verified tumor xenograft model. Ropivacaine markedly impeded viability concentration‐dependent manner. Compared or alone, cell proliferation, facilitated apoptosis, enhanced cleaved caspase‐3, caspase‐9, cyclin D1 expression, while it reduced IL‐6 p‐STAT3 expression inhibited growth vivo. Importantly, activation IL‐6/STAT3 pathway could reverse repressive stimulative effects cells. In summary, synergistically induces sorafenib‐stimulated via pathway. is drug for when sorafenib.

Язык: Английский

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