ArticleCell death & disease2021
Gemcitabine and APG-1252, a novel small molecule inhibitor of BCL-2/BCL-XL, display a synergistic antitumor effect in nasopharyngeal carcinoma through the JAK-2/STAT3/MCL-1 signaling pathway.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Nasopharyngeal carcinoma: epidemiology, risk factors, signaling pathways, clinical features, diagnosis, and management.Molecular biomedicine · 2026Review
- The use of venetoclax in the treatment of acute lymphoblastic leukemia-a systematic review.Therapeutic advances in medical oncology · 2026Review
- Understanding the Tumor Microenvironment and Therapy Resistance in Head and Neck Squamous Cell Carcinoma.Cells · 2025Review
- Apoptosis regulators of the Bcl-2 family play a key role in chemoresistance of cholangiocarcinoma organoids.International journal of cancer · 2025Article
- Dextromethorphan Enhances Apoptosis and Suppresses EMT in PANC-1 Pancreatic Cancer Cells: Synergistic Effects with Gemcitabine.International journal of molecular sciences · 2025Article
- Oleuropein regulates ubiquitination-mediated Mcl-1 turnover and exhibits antitumor activity.Cancer gene therapy · 2025Article
- SYT7 accelerates nasopharyngeal carcinoma progression via ALDH1A3-mediated STAT3 signaling activation.Oncogenesis · 2025Article
- Chlorophyllin exerts synergistic anti-tumor effect with gemcitabine in pancreatic cancer by inducing cuproptosis.Molecular medicine (Cambridge, Mass.) · 2025Article
- The novel BCL-2/BCL-XL inhibitor APG-1252-mediated cleavage of GSDME enhances the antitumor efficacy of HER2-targeted therapy in HER2-positive gastric cancer.Acta pharmacologica Sinica · 2025Article
- Blockage of BCL-XL overcomes venetoclax resistance across BCL2+ lymphoid malignancies irrespective of BIM status.Blood advances · 2024Article
- G3BP1 Interact with JAK2 mRNA to Promote the Malignant Progression of Nasopharyngeal Carcinoma via Activating JAK2/STAT3 Signaling Pathway.International journal of biological sciences · 2024Article
- Current Advances and Future Strategies for BCL-2 Inhibitors: Potent Weapons against Cancers.Cancers · 2023Review
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- Targeted therapy for head and neck cancer: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Mcl-1 levels critically impact the sensitivities of human colorectal cancer cells to APG-1252-M1, a novel Bcl-2/Bcl-XNeoplasia (New York, N.Y.) · 2022Article
- Nanoengineering a metal-organic framework for osteosarcoma chemo-immunotherapy by modulating indoleamine-2,3-dioxygenase and myeloid-derived suppressor cells.Journal of experimental & clinical cancer research : CR · 2022Article
- Protein-protein interactions between RUNX3 and ZEB1 in chronic lung injury induced by methamphetamine abuse.Frontiers in pharmacology · 2022Article
- Relationship between miR-338-3p and Clinicopathological Parameters, Prognosis, and STAT3 mRNA Expression in Nasopharyngeal Carcinoma.Evidence-based complementary and alternative medicine : eCAM · 2021Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis, with an unfavorable response to palliative chemotherapy. Unfortunately, there are few effective therapeutic regimens. Therefore, we require novel treatment strategies with enhanced efficacy. The present study aimed to investigate the antitumor efficacy of APG-1252-M1, a dual inhibitor of BCL-2/BCL-XL, as a single agent and combined with gemcitabine. We applied various apoptotic assays and used subcutaneous transplanted NPC model to assess the in vitro and in vivo antitumor activity. Moreover, phospho-tyrosine kinase array was used to investigate the combined therapy's potential synergistic mechanism. In addition, further validation was performed using immunohistochemistry and western blotting. In vitro, we observed that APG-1252-M1 had moderate antitumor activity toward NPC cells; however, it markedly improved gemcitabine's ability to promote NPC cell apoptosis and suppress invasion, migration, and proliferation. Specifically, APG-1252 plus gemcitabine exhibited even remarkable antitumor activity in vivo. Mechanistically, the drug combination synergistically suppressed NPC by activating caspase-dependent pathways, blocking the phospho (p)-JAK-2/STAT3/MCL-1 signaling pathway, and inhibiting epithelial-mesenchymal transition. In conclusion, the results indicated that the combination of APG-1252 and gemcitabine has synergistic anticancer activities against NPC, providing a promising treatment modality for patients with NPC.
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