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
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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