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经离子辐射生存的三阴性乳腺癌细胞表现出一个依赖轴的侵袭性耐辐射表型

Jianfeng Ji¹, Yuqin Ding², Yue Kong³

¹Department of Nuclear Medicine, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China.

Experimental and therapeutic medicine

|August 24, 2023

概括

向Axl,这是一种在三阴性乳腺癌 (TNBC) 中高度表达的蛋白质,与放射治疗相结合,显著减少了瘤细胞的攻击性行为和生长. 这种组合疗法在治疗耐辐射TNBC方面表现有前途.

科学领域:

在瘤学瘤学.
辐射瘤学辐射瘤学
分子生物学分子生物学

背景情况:

三阴性乳腺癌 (TNBC) 呈现出侵略性行为和对治疗的抗性.
轴受体氨酸激酶在TNBC中经常过度表达,并与恶性瘤有关.
电离辐射可以诱导TNBC细胞的抗性,需要新的治疗策略.

研究的目的:

为了研究辐射生存TNBC细胞的攻击性行为.
探索Axl作为一种潜在的治疗点,与TNBC的放射治疗相结合.
阐明TNBC中放射电阻背后的分子机制.

主要方法:

建立一种抗电离辐射的TNBC细胞系 (4T-1/IRR).
评估细胞活力,殖民地形成,DNA修复,入侵和迁移.
在体外和体内使用Axl抑制 (R428,shRNA) 与X射线照射相结合的研究.
西部涂抹用于分析PI3K/Akt/mTOR信号通路.

主要成果:

在耐辐射4T-1/IRR细胞中,轴表达被上调.
结合Axl抑制和放射治疗显著降低了TNBC细胞活力,殖民地形成,DNA修复和侵入性.
在体内研究表明,R428和放射治疗的联合使用显著抑制了异种移植瘤的生长.
确定PI3K/Akt/mTOR通路的轴激活是放射电阻的一个关键机制.

结论:

有针对性的轴阻与放射治疗相结合,有效地克服了TNBC中的放射电阻.
PI3K/Akt/mTOR通路在轴介导的电阻中起着至关重要的作用.
针对Axl和放射治疗的组合疗法在TNBC治疗中具有显著的治疗潜力.

关键词:

标签: 活动活动活动在 Axl Axl 轴上电离辐射的电阻电阻.在PI3K中,PI3K是指PI3K.三重阴性乳腺癌是什么

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