ArticleCell death & disease2018
ID1-induced p16/IL6 axis activation contributes to the resistant of hepatocellular carcinoma cells to sorafenib.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial.Journal of cancer research and clinical oncology · 2022Trial
- NHSL3 knockout modulates sorafenib response, growth, and motility in hepatocellular carcinoma cell models.Molecular biology reports · 2026Article
- Chemotherapy Enrichment of ID Family Expression Is Associated with IL-6 Signaling in Ovarian Cancer.Cancers · 2026Article
- Cancer and aging: complex associations and therapeutic targets.Molecular biomedicine · 2026Review
- Disproportionality Analysis of Hematologic Adverse Event Signals Associated with Venetoclax in Combination with Senescence-Inducing Chemotherapy.Journal of clinical medicine · 2026Article
- Targeting MED8 enhances sorafenib sensitivity in hepatocellular carcinoma by disrupting epithelial-mesenchymal transition mechanisms.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- The efficacy of sorafenib against hepatocellular carcinoma is enhanced by 5-aza-mediated inhibition of ID1 promoter methylation.FEBS open bio · 2024Article
- A real-world study and network pharmacology analysis of EGFR-TKIs combined with ZLJT to delay drug resistance in advanced lung adenocarcinoma.BMC complementary medicine and therapies · 2023Article
- Article
- Sorafenib, rapamycin, and venetoclax attenuate doxorubicin-induced senescence and promote apoptosis in HCT116 cells.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Review
- The BAFF/NFκB axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts.Cancer science · 2021Article
- SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma.Biomarker research · 2021Article
- Review
- Adaptive response of resistant cancer cells to chemotherapy.Cancer biology & medicine · 2020Review
- Inhibitor of Differentiation 1 (ID1) Facilitates the Efficacy of Sorafenib in Non-Small Cell Lung Cancer Cells through Suppressing Epithelial to Mesenchymal Transition.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy.International journal of medical sciences · 2020Review
- High Expression ofDisease markers · 2019Article
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib is the only approved drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its efficacy is limited by the emergence of primary and/or acquired resistance. Senescence-associated secretory phenotype (SASP)-mediated chemo-resistance, which depends on the secreted bioactive molecules, has attracted increasing attention but never revealed in HCC. In this study, we investigated the effect of SASP-related p16/IL6 axis on sorafenib resistance in HCC. Initially, we noticed that HCC cells with a high level of p16/IL6 axis exhibited a low sensitivity to sorafenib. Further in vivo and in vitro studies demonstrated that such a primary resistance resulted from ID1-mediated activation of p16/IL6 axis. Overexpression of ID1 or IL6 blocking in sorafenib-resistant HCC cells could increase the cytotoxicity of sorafenib. Moreover, SASP-related p16/IL6 axis contributed to the formation of acquired resistance in cells received long-term exposure to sorafenib. In acquired sorafenib-resistant cells, ID1 low expression, p16/IL6 axis up-regulation, and AKT phosphorylation activation were observed. A reduced cytotoxicity of sorafenib was detected when sorafenib-sensitive cells incubated with conditioned media from the resistant cells, accompanied by the stimulation of AKT phosphorylation. The reversal of sorafenib resistance could be achieved through ID1 overexpression, IL6 blocking, and AKT pathway inhibition. Our study reveals that SASP-related p16/IL6 axis activation is responsible for sorafenib resistance, which will be a novel strategy to prevent the drug resistance.
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