ArticlePloS one2019
Tumor growth suppression using a combination of taxol-based therapy and GSK3 inhibition in non-small cell lung cancer.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 27 citations in OpenAlex.
- Harnessing GSK-3β inhibition for lung cancer therapy: emerging opportunities and challenges.Medical oncology (Northwood, London, England) · 2025Review
- Inhibition of GSK3β is synthetic lethal with FHIT loss in lung cancer by blocking homologous recombination repair.Experimental & molecular medicine · 2025Article
- Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology.Cellular and molecular neurobiology · 2024Article
- Concurrent targeting of GSK3 and MEK as a therapeutic strategy to treat pancreatic ductal adenocarcinoma.Cancer science · 2024Article
- GSK3B inhibition reduced cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Biphasic function of GSK3β in gefitinib‑resistant NSCLC with or without EGFR mutations.Experimental and therapeutic medicine · 2023Article
- The Proliferation of Pre-Pubertal Porcine Spermatogonia in Stirred Suspension Bioreactors Is Partially Mediated by the Wnt/β-Catenin Pathway.International journal of molecular sciences · 2021Article
- Tilting MYC toward cancer cell death.Trends in cancer · 2021Review
- CHIR99021, trough GSK-3β Targeting, Reduces Epithelioid Sarcoma Cell Proliferation by Activating Mitotic Catastrophe and Autophagy.International journal of molecular sciences · 2021Article
- Isochorismatase domain-containing protein 1 (ISOC1) participates in DNA damage repair and inflammation-related pathways to promote lung cancer development.Translational lung cancer research · 2021Article
- Immune checkpoint inhibition in syngeneic mouse cancer models by a silicasome nanocarrier delivering a GSK3 inhibitor.Biomaterials · 2021Article
- GSK-3 Inhibition Modulates Metalloproteases in a Model of Lung Inflammation and Fibrosis.Frontiers in molecular biosciences · 2021Article
- Wnt/β-Catenin Inhibition Disrupts Carboplatin Resistance in Isogenic Models of Triple-Negative Breast Cancer.Frontiers in oncology · 2021Article
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Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Glycogen synthase kinase-3 (GSK3) is over-expressed and hyperactivated in non-small cell lung carcinoma (NSCLC) and plays a role in ensuring the correct alignment of chromosomes on the metaphase plate during mitosis through regulation of microtubule stability. This makes the enzyme an attractive target for cancer therapy. We examined the effects of a selective cell-permeant GSK3 inhibitor (CHIR99021), used alone or in combination with paclitaxel, using an in vitro cell growth assay, a quantitative chromosome alignment assay, and a tumor xenograft model. CHIR99021 inhibits the growth of human H1975 and H1299 NSCLC cell lines in a synergistic manner with paclitaxel. CHIR99021 and paclitaxel promoted a synergistic defect in chromosomal alignment when compared to each compound administered as monotherapy. Furthermore, we corroborated our in vitro findings in a mouse tumor xenograft model. Our results demonstrate that a GSK3 inhibitor and paclitaxel act synergistically to inhibit the growth of NSCLC cells in vitro and in vivo via a mechanism that may involve converging modes of action on microtubule spindle stability and thus chromosomal alignment during metaphase. Our findings provide novel support for the use of the GSK3 inhibitor, CHIR99021, alongside taxol-based chemotherapy in the treatment of human lung 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.