ArticleCancer management and research2018
Low-dose eribulin mesylate exerts antitumor effects in gastric cancer by inhibiting fibrosis via the suppression of epithelial-mesenchymal transition and acts synergistically with 5-fluorouracil.
Article in Cancer management and research, 2018. 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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15 citing papers in PubMed, 16 citations in OpenAlex.
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- Regulatory role of the transforming growth factor-β signaling pathway in the drug resistance of gastrointestinal cancers.World journal of gastrointestinal oncology · 2021Review
- Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts.Nature communications · 2021Article
- Hypoxia and the phenomenon of immune exclusion.Journal of translational medicine · 2021Review
- Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications.Frontiers in molecular biosciences · 2021Review
- Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches.International journal of molecular sciences · 2020Review
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- The Paradox of Cancer Immune Exclusion: Immune Oncology Next Frontier.Cancer treatment and research · 2020Article
- Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer.Cancer management and research · 2019Article
- MicroRNA-3662 targets ZEB1 and attenuates the invasion of the highly aggressive melanoma cell line A375.Cancer management and research · 2019Article
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10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCharacterized by aggressive proliferation, extensive stromal fibrosis, and resulting drug resistance, peritoneal dissemination in gastric cancer remains associated with poor prognosis. Interaction between cancer and stromal cells accelerates tumor progression via epithelial-mesenchymal transition (EMT), which is one of the major causes of tissue fibrosis, and human peritoneal mesothelial cells (HPMCs) play important roles as cancer stroma in peritoneal dissemination. Transforming growth factor-β (TGF-β) has a pivotal function in the progression of EMT, and Smad proteins play an important role in the TGF-β signaling pathway. Eribulin mesylate (eribulin), a nontaxane microtubule dynamics inhibitor used for the treatment of advanced breast cancer, inhibits EMT changes in triple-negative breast cancer cells. We examined its ability to inhibit tumor progression and EMT changes resulting from the interaction between gastric cancer cells and HPMCs and to act synergistically with 5-fluorouracil (5-FU), a key drug for gastric cancer. MATERIALS AND
methodsProliferation of gastric cancer cells and HPMCs isolated from healthy omentum was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Following gastric cancer cell/HPMC coculture, EMT markers were detected by immunofluorescence, immunohistochemistry, and Western blotting; invasion assays were performed; and TGF-β and Smad phosphorylation were assessed by Western blotting and enzyme-linked immunosorbent assay. A mouse fibrotic tumor xenograft model was established using gastric cancer cell/HPMC cocultures. The effect of eribulin and/or 5-FU was tested in each case.
resultsEribulin significantly suppressed gastric cancer cell proliferation and EMT changes in MKN-45 gastric cancer cells and HPMCs induced by their interaction in vitro. Eribulin inhibited EMT at much lower concentrations (≥0.5 nM for MKN-45 and ≥0.1 nM for HPMCs) than its half maximal inhibitory concentrations (2.2 nM for MKN-45 and 8.1 nM for HPMCs), and this resulted, at least partly, from the downregulation of TGF-β/Smad signaling. Eribulin administration of ≥0.1 mg/kg suppressed tumor progression (0.1 mg/kg,
conclusionLow-dose eribulin combined with 5-FU might be a promising therapy for peritoneal dissemination in gastric cancer.
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