ArticleInternational journal of biological sciences2018
PKM2 Inhibitor Shikonin Overcomes the Cisplatin Resistance in Bladder Cancer by Inducing Necroptosis.
Article in International journal of biological sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Natural products targeting glycolysis in cancer.Frontiers in pharmacology · 2022Pooled it
- The evolving landscape of the Warburg effect in gastric cancer: From molecular mechanisms to targeted therapy.Clinical and translational medicine · 2026Review
- Targeting AIF to trigger RIPKs/MLKL necroptosis: a disulfiram-based strategy to reverse paclitaxel resistance in ovarian cancer.Cell communication and signaling : CCS · 2026Article
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- PKM2-driven glycolysis mediates rotenone neurotoxicity via MG-Hs in Parkinson's disease.Scientific reports · 2026Article
- Circular RNA hsa-circ-0001030 suppresses proliferation and cisplatin tolerance in TSCC via interaction with PKM2.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- MMP14-Dependent Activation of TGF-β Signaling Enhances Malignancies via Promoting Necroptosis in Glioblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Article
- Transition between cell states of sensitivity reveals molecular vulnerability of drug-tolerant cells.Molecular systems biology · 2025Article
- Myeloid metabolism and its role in immunotherapy of cancer.Journal for immunotherapy of cancer · 2025Review
- Lactylation in cancer: Advances and opportunities for treatment resistance.Clinical and translational medicine · 2025Review
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- PKM2 modulates chemotherapy sensitivity by regulating autophagy and predicts the prognosis and immunity in pancancer.Scientific reports · 2025Article
- Warburg effect and lactylation in cancer: mechanisms for chemoresistance.Molecular medicine (Cambridge, Mass.) · 2025Review
- Nanomedicines Targeting Metabolic Pathways in the Tumor Microenvironment: Future Perspectives and the Role of AI.Metabolites · 2025Review
- SRT3025-loaded cell membrane hybrid liposomes (3025@ML) enhanced anti-tumor activity of Oxaliplatin via inhibiting pyruvate kinase M2 and fatty acid synthase.Lipids in health and disease · 2025Article
- Construction and immunohistochemical validation of a necroptosis-related prognostic signature in bladder cancer and its association with tumor immune infiltration.Frontiers in genetics · 2025Article
- Systematic bioinformatics analysis identifies shikonin as a novel mTOR pathway inhibitor in triple-negative breast cancer progression.Frontiers in pharmacology · 2025Article
- The multifaceted roles and diagnostic-therapeutic potential of LINC01410 in malignant tumors and non-malignant disorders.Frontiers in immunology · 2025Review
- Hydrogen peroxide and cisplatin regulate the ROS/PKM2 pathway to affect the growth of cancer.American journal of cancer research · 2025Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cisplatin-based chemotherapy often results in the development of chemo-resistance when used to treat bladder cancer (BC), which is difficult to overcome. Recent data indicate that pyruvate kinase M2 (PKM2), a glycolytic enzyme for Warburg effect, is strongly upregulated in BC, and contributes to the cisplatin resistance in BC. However, the underlying mechanisms remain unclear. In this study, we also found that the expression level of PKM2 is also higher in cisplatin resistant BC cells and tumors. Down-regulation of PKM2 by siRNA or inhibition of PKM2 by shikonin re-sensitized the cisplatin resistant T24 cells. Shikonin and cisplatin together exhibit significantly greater killing effects than when used alone. Interestingly, we found shikonin kills the T24 cisplatin resistant cells by inducing necroptosis, as the cell death could not inhibited by apoptosis inhibitor, z-VAD, but compromised by RIP3 inhibitor, GSK872, or RIP3 siRNA. In contrast, shikonin induced apoptosis in T24 parental cells. We further investigate the underlying mechanism, and found that the dysregulation of Bcl-2 family proteins, including Bcl-2, PUMA, Bax, play an important role in deciding that shikonin kills the BC cells by necroptosis or apoptosis. Collectively, our results suggested that inducing necroptosis is an alternative way to overcome the apoptosis resistant in BC therapy, and orchestrating the regulation of Bcl-2, PUMA, and Bax in BC cisplatin resistant cells may improve the therapy effect of cisplatin in BC tumor.
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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.