Evaluation of BMP-2 as a Differentiating and Radiosensitizing Agent for Colorectal Cancer Stem Cells

Background: Despite effective clinical responses, a large proportion of patients undergo resistance to radiotherapy. The low response rate to current treatments in different stages of colorectal cancer depends on the prominent role of stem cells in cancer. Objective: In the present study, the role of BMP-2 as an ionizing radiation-sensitive factor in colorectal cancer cells was investigated. Methods: A sphere formation assay was used for the enrichment of HCT-116 cancer stem cells (CSCs). The effects of combination therapy (BMP-2+ radiation) on DNA damage response (DDR), proliferation, and apoptosis were evaluated in HCT-116 and CSCs. Gene expressions of CSCs and epithelialmesenchymal transition (EMT) markers were also evaluated. Results: We found that the sphere formation assay showed a significant increase in the percentage of CSCs. Moreover, expression of CSCs markers, EMT-related genes, and DNA repair proteins significantly decreased in HCT-116 cells compared to the CSCs group after radiation. In addition, BMP-2 promoted the radiosensitivity of HCT-116 cells by decreasing the survival rate of the treated cells at 2, 4, and 6 Gy compared to the control group in HCT-116 cells. Conclusion: Our findings indicated that BMP-2 could affect numerous signaling pathways involved in radioresistance. Therefore, BMP-2 can be considered an appealing therapeutic target for the treatment of radioresistant human colorectal cancer.