Effect of eribulin, a new microtubule dynamics inhibitor, for tumor progression and fibrosis in peritoneal dissemination of gastric cancer
| Project/Area Number |
15K21015
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
Tumor therapeutics
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 胃癌 / 腹膜播種 / 上皮間葉転換 / 線維化 / 低濃度エリブリン / TGFβ / smad シグナル伝達 / 線維化腫瘍 / エルブリン / ＥＭＴ / スキルス胃癌 / 微小管阻害薬 |
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| Outline of Final Research Achievements |
Peritoneal dissemination of gastric cancer is characterized by aggressive invasion, extensive stromal fibrosis, and resulting drug-resistant tumors. We examined whether eribulin, which is a newly microtubule dynamics inhibitor, could inhibit progression and EMT changes in gastric cancer and act synergistically with 5FU. Eribulin significantly suppressed gastric cancer cell proliferation, as well as EMT changes in MKN45 gastric cancer cells and HPMCs induced by their interaction in vitro. EMT inhibition by eribulin was observed at much lower concentrations than its IC50 and resulted, at least partly, from downregulation of TGF-β/Smad signaling by interruption of Smad2 phosphorylation. Eribulin also suppressed tumor progression and fibrosis in a mouse fibrotic tumor xenograft model. Furthermore, its administration with 5FU brought about synergistic antitumor effects. Eribulin demonstrates the potential to be a key treatment for peritoneal dissemination of gastric cancer.
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Report
(3 results)
Research Products
(1 results)
