表儿茶素下调MMP-9可提高非小细胞肺癌的放射敏感性

Anao Wu, Yongmei He, Huahua Zhou, Nan Huang, Hongying Xu, Jie Xia, Lv Zengbo, Meifang Huang
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引用次数: 0

摘要

背景和目的:放射治疗是非小细胞肺癌(NSCLC)的重要治疗手段,但其有效性受到肿瘤细胞对放射线耐受性的限制。本研究旨在评估表儿茶素(EC)对非小细胞肺癌放射敏感性的影响,并确定其与基质金属蛋白酶(MMP)-9的关系:方法:用Western印迹法检测MMP-9的表达,用免疫荧光法检测DNA损伤标志蛋白的表达。使用 CCK-8 检测法评估细胞活力,使用克隆生成检测法评估细胞增殖。流式细胞术用于确定细胞凋亡,而细胞迁移和侵袭则通过透孔试验进行检测。用电离辐射(IR)和氨基甲酸乙酯处理细胞,以验证氨基甲酸乙酯对放射治疗的增敏作用:结果:MMP-9在NSCLC细胞和组织中表达升高。结果:MMP-9在NSCLC细胞和组织中表达升高,DNA损伤和细胞凋亡增加,而细胞活力、增殖、迁移和侵袭在IR后显著下降。MMP-9的敲除加强了IR对细胞生物学行为的影响。EC+IR对促进DNA损伤和NSCLC细胞生物学行为的效果最好;相反,MMP-9的过表达削弱了EC的作用:本研究表明,EC能下调MMP-9的表达,促进DNA损伤,降低细胞活力、增殖、迁移和侵袭,并促进细胞凋亡,因此具有作为NSCLC放射增敏剂的潜力。
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Downregulation of MMP-9 by epicatechin can improve the radiosensitivity of non-small cell lung cancer.

Background and purpose: Radiation therapy is a crucial treatment for nonsmall cell lung cancer (NSCLC), but its effectiveness is limited by the resistance of tumor cells to radiation. This study aimed to evaluate the effect of epicatechin (EC) on radiosensitivity in NSCLC and to determine its relationships with matrix metalloproteinase (MMP)-9.

Methods: MMP-9 expression was detected by Western blotting, and the expression of the DNA damage marker protein was detected by immunofluorescence. Cell viability was assessed using the CCK-8 assay, and cell proliferation was evaluated using the clonogenesis assay. Flow cytometry was used to determine the cell apoptosis, whereas cell migration and invasion were detected using the transwell assays. The cells were treated with ionizing radiation (IR) and EC to verify the sensitizing effect of EC on radiation therapy.

Results: MMP-9 expression was elevated in the NSCLC cells and tissues. DNA damage and cell apoptosis were increased, whereas cell vigor, proliferation, migration, and invasion were significantly decreased after IR. MMP-9 knockdown strengthened the impact of IR on the biological behaviors of the cells. EC + IR had the best effect on promoting DNA damage and the biological behaviors of the NSCLC cells; alternatively, the overexpression of MMP-9 weakened the role of EC.

Conclusions: This study shows that EC can downregulate MMP-9 expression, promote DNA damage, reduce cell viability, proliferation, migration, and invasion, and facilitate cell apoptosis, thus, showing potential as a radiosensitizer for NSCLC.

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