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In cancer cell lines inhibition of SCF/c-Kit pathway leads to radiosensitization only when SCF is strongly over-expressed
- Source :
- Clinical and Translational Radiation Oncology, Vol 2, Iss C, Pp 69-75 (2017), Clinical and Translational Radiation Oncology
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Background and purpose The SCF/c-Kit pathway is often overexpressed in human tumors leading to an enhanced tumorigenesis, proliferation and migration. It was now tested for NSCLC and prostate cancer cells growing in 2D and 3D whether the inhibition of this pathway can be used to achieve a significant radiosensitization and whether a respective biomarker may be identified. Material and methods Experiments were performed with different cancer cell lines (NSCLC: H23, H520, H226, H1975 and PrCa: DU145) growing either under 2D or 3D conditions. Expression of SCF and c-Kit was determined by RT-PCR and Western blot, SCF was knocked down by siRNA, c-Kit was inhibited by ISCK03 inhibitor and cell survival was determined by colony formation assay. Results There is a profound variation in the expression of both c-Kit and SCF with no association between each other. Neither levels did correlate with the respective cellular radiosensitivity determined for 2D or 3D with only a trend seen for SCF. Knock-down of SCF was generally found to result in no or only minor reduction of plating efficiency or cellular radioresistance. A significant reduction was only obtained for H520 cells characterized by an extreme over-expression of SCF. The inhibition of c-Kit by a specific inhibitor was also found to result only in minor radiosensitization. Conclusion Generally, the SCF/c-Kit pathway does not have a dominant effect on both, cell survival and radioresponse and, as a consequence, knockdown of this pathway does not result in a strong effect on radioresistance, except when SCF is strongly over-expressed.
- Subjects :
- 0301 basic medicine
Plating efficiency
R895-920
Clonogenic survival
Biology
medicine.disease_cause
NSCLC
Article
03 medical and health sciences
3D cell culture
Prostate cancer
Medical physics. Medical radiology. Nuclear medicine
0302 clinical medicine
DU145
Western blot
Radioresistance
medicine
Radiology, Nuclear Medicine and imaging
RC254-282
Gene knockdown
medicine.diagnostic_test
X-irradiation
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
030104 developmental biology
Oncology
SCF/c-Kit pathway
030220 oncology & carcinogenesis
Immunology
Cancer research
Carcinogenesis
Subjects
Details
- ISSN :
- 24056308
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- Clinical and Translational Radiation Oncology
- Accession number :
- edsair.doi.dedup.....3707b987018483055cac8c875440fa28
- Full Text :
- https://doi.org/10.1016/j.ctro.2017.02.001