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

Cancer Management and Research
Toru KurataTetsuo Ohta

Abstract

Characterized 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. Proliferation 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...Continue Reading

Citations

Jan 2, 2021·International Journal of Molecular Sciences·Joanna KozakJacek Baj
Jan 8, 2021·Journal of Translational Medicine·Violena Pietrobon, Francesco M Marincola
Feb 16, 2021·Frontiers in Immunology·Violena PietrobonJakob Nikolas Kather
Aug 24, 2021·Frontiers in Molecular Biosciences·Huichen ZhaoXiao-Bing Chen

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Methods Mentioned

BETA
xenograft
electrophoresis
fluorescence microscopy

Software Mentioned

SPSS

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