ArticleThe Prostate2014
Inhibition of constitutively active Stat3 reverses enzalutamide resistance in LNCaP derivative prostate cancer cells.
Article in The Prostate, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
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Who cites it
72 citing papers in PubMed, 100 citations in OpenAlex.
- Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy.The Prostate · 2020Trial
- The JAK/STAT pathway: key mechanism in gene activation, disease regulation, and emerging therapeutic targets.Molecular biology reports · 2026Review
- Myosteatosis Predicts Poor Prognosis in Patients With Castration-Resistant Prostate Cancer Treated With Enzalutamide.International journal of urology : official journal of the Japanese Urological Association · 2026Article
- Prostate Cancer: Etiology, Diagnosis, and Treatment.Serican journal of medicine · 2026Article
- Dynamic Reprogramming of Immune-Related Signaling During Progression to Enzalutamide Resistance in Prostate Cancer.Cancers · 2025Article
- Article
- Transcriptional profiling clarifies a program of enzalutamide extreme non-response in lethal prostate cancer.NPJ precision oncology · 2025Article
- pSTAT3 Expression is Increased in Advanced Prostate Cancer in Post-Initiation of Androgen Deprivation Therapy.The Prostate · 2025Article
- The role of proinflammatory cytokines and CXC chemokines (CXCL1-CXCL16) in the progression of prostate cancer: insights on their therapeutic management.Cellular & molecular biology letters · 2024Review
- Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation.Cancer metastasis reviews · 2024Review
- The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance.Current topics in medicinal chemistry · 2024Review
- Crossroad between the Heat Shock Protein and Inflammation Pathway in Acquiring Drug Resistance: A Possible Target for Future Cancer Therapeutics.Biomedicines · 2023Review
- Effectiveness of tumor‑treating fields to reduce the proliferation and migration of liposarcoma cell lines.Experimental and therapeutic medicine · 2023Article
- Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.Signal transduction and targeted therapy · 2023Review
- LOX-1 Activation by oxLDL Induces AR and AR-V7 Expression via NF-κB and STAT3 Signaling Pathways Reducing Enzalutamide Cytotoxic Effects.International journal of molecular sciences · 2023Article
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- STL127705 synergize with olaparib in castration-resistant prostate cancer by inhibiting homologous recombination and non-homologous end-joining repair.American journal of cancer research · 2023Article
- Zhoushi Qiling decoction inhibits proliferation of human prostate cancer cells through IL6/STAT3 pathway.Journal of Cancer · 2023Article
- Molecular and cellular paradigms of multidrug resistance in cancer.Cancer reports (Hoboken, N.J.) · 2022Review
- The Potential Neuroprotective Effects of Extracts from Oat Seedlings against Alzheimer's Disease.Nutrients · 2022Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeUse of enzalutamide has improved the treatment of advanced prostate cancer. However, resistance to enzalutamide can develop frequently in initial responders. This study aimed to test whether overexpression of IL-6 and constitutive activation of Stat3 in prostate cancer cells increase resistance to enzalutamide. EXPERIMENTAL
designSensitivity of prostate cancer cells to enzalutamide was tested using cell growth assays and clonogenic assays. Quantitative reverse transcription-PCR, ELISA, and Western blotting were performed to detect expression levels of IL-6, c-Myc, survivin, and AR. Expression of Stat3 was downregulated using siRNA specific to Stat3. ChIP assay was performed to examine recruitment of AR to the PSA promoter.
resultsProstate cancer cells expressing autocrine IL-6 are resistant to enzalutamide and autocrine IL-6 leads to constitutive activation of Stat3 and its target genes. Down regulation of Stat3 led to an increase in sensitivity of prostate cancer cells to enzalutamide. Overexpression of constitutively active Stat3 in prostate cancer cells induced resistance to enzalutamide treatment. Constitutively active Stat3 also enhanced the recruitment of AR to PSA promoter which could not be disrupted by enzalutamide. The Stat3 inhibitor AG490 reversed enzalutamide resistance in prostate cancer cells, while combination treatment with enzalutamide and AG490 significantly inhibited cell growth and induced cell apoptosis.
conclusionsThis study demonstrates that the autocrine IL-6 pathway induces enzalutamide resistance in prostate cancer cells via the constitutive activation of Stat3. Co-targeting IL6-Stat3 pathway with enzalutamide may be utilized for treatment of advanced prostate cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.