Targeting the Hedgehog pathway in combination with X‑ray or carbon ion radiation decreases migration of MCF‑7 breast cancer cells
Autor: | Bjorn Baselet, Sarah Baatout, Randy Vermeesen, Greta Lamers, Ann Janssen, Karin Haustermans, Marjan Moreels, Sofie Isebaert, Niels Belmans, Katrien Konings |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research cell migration Pyridines medicine.medical_treatment X-Ray Therapy THERAPY Radiation Tolerance radiosensitisation Hedgehog pathway carbon ion irradiation 0302 clinical medicine Cell Movement Chemoradiotherapy EPITHELIAL-MESENCHYMAL TRANSITION Hedgehog signaling pathway PROSTATE-CANCER Oncology 030220 oncology & carcinogenesis MCF-7 Cells SIGNALING PATHWAY Life Sciences & Biomedicine RADIOTHERAPY Signal Transduction EXPRESSION Cell Survival INHIBITION Breast Neoplasms Heavy Ion Radiotherapy Biology 03 medical and health sciences Breast cancer Cell Line Tumor Radioresistance medicine Humans Hedgehog Proteins Radiosensitivity GANT61 Cell Proliferation Science & Technology SONIC HEDGEHOG Gene Expression Profiling Cancer medicine.disease IRRADIATION Radiation therapy Pyrimidines 030104 developmental biology MCF-7 Cancer cell gene expression Cancer research VISMODEGIB |
Zdroj: | International Journal of Oncology. |
ISSN: | 1791-2423 1019-6439 1339-1348 |
Popis: | The use of carbon ion therapy for cancer treatment is becoming more widespread due to the advantages of carbon ions compared with X‑rays. Breast cancer patients may benefit from these advantages, as the surrounding healthy tissues receive a lower dose, and the increased biological effectiveness of carbon ions can better control radioresistant cancer cells. Accumulating evidence indicates that the Hedgehog (Hh) pathway is linked to the development and progression of breast cancer, as well as to resistance to X‑irradiation and the migratory capacity of cancer cells. Hence, there is an increasing interest in targeting the Hh pathway in combination with radiotherapy. Several studies have already investigated this treatment strategy with conventional radiotherapy. However, to the best of our knowledge, the combination of Hh inhibitors with particle therapy has not yet been explored. The aim of the present study was to investigate the potential of the Hh inhibitor GANT61 as an effective modulator of radiosensitivity and migration potential in MCF‑7 breast cancer cells, and compare potential differences between carbon ion irradiation and X‑ray exposure. Although Hh targeting was not able to radiosensitise cells to any radiation type used, the combination of GANT61 with X‑rays or carbon ions (energy: 95 MeV/n; linear energy transfer: 73 keV/µm) was more effective in decreasing MCF‑7 cell migration compared with either radiation type alone. Gene expression of the Hh pathway was affected to different degrees in response to X‑ray and carbon ion irradiation, as well as in response to the combination of GANT61 with irradiation. In conclusion, combining Hh inhibition with radiation (X‑rays or carbon ions) more effectively decreased breast cancer cell migration compared with radiation treatment alone. ispartof: INTERNATIONAL JOURNAL OF ONCOLOGY vol:55 issue:6 pages:1339-1348 ispartof: location:Greece status: published |
Databáze: | OpenAIRE |
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