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

IF 2.1 4区医学 Q4 CELL & TISSUE ENGINEERING

Current stem cell research & therapy Pub Date : 2024-01-01 DOI:10.2174/1574888X18666230330085615

Roghayeh Mahmoudi, Saeid Afshar, Razieh Amini, Akram Jalali, Massoud Saidijam, Rezvan Najafi

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Abstract

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.

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BMP-2作为结直肠癌干细胞的分化和放射增敏剂的评价。

背景：尽管临床反应有效，但仍有很大一部分患者对放疗产生耐药性。癌症不同阶段对当前治疗的低反应率取决于干细胞在癌症中的突出作用。目的：探讨BMP-2作为一种电离辐射敏感因子在结直肠癌癌症细胞中的作用。方法：采用球体形成法富集癌症干细胞（CSCs）。在HCT-116和CSCs中评估联合治疗（BMP-2+辐射）对DNA损伤反应（DDR）、增殖和细胞凋亡的影响。还评估了CSC和上皮-间质转移（EMT）标志物的基因表达。结果：我们发现球体形成试验显示CSCs的百分比显著增加。此外，与辐射后的CSCs组相比，HCT-116细胞中CSCs标记物、EMT相关基因和DNA修复蛋白的表达显著降低。此外，与对照组相比，BMP-2通过降低HCT-116细胞在2、4和6Gy时的存活率来提高HCT-116的放射敏感性。结论：我们的研究结果表明，BMP-2可以影响许多参与放射抵抗的信号通路。因此，BMP-2可以被认为是治疗具有放射性耐药性的人类癌症的一个有吸引力的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current stem cell research & therapy CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

4.20

自引率

3.70%

发文量

197

审稿时长

>12 weeks

期刊介绍： Current Stem Cell Research & Therapy publishes high quality frontier reviews, drug clinical trial studies and guest edited issues on all aspects of basic research on stem cells and their uses in clinical therapy. The journal is essential reading for all researchers and clinicians involved in stem cells research.