拉利特雷克塞德通过激活ROS介导的ER应激通过阻碍前列腺癌细胞中的HSPA8表达来诱导亡
Yan Tao1, Jianzhong Lu1, Lanlan Li1
1Institute of Urology, Clinical Research Center for Urology in Gansu Province, Key Laboratory of Urological Disease in Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, China; The Second Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou 730030, China.
Biochimica et biophysica acta. Molecular cell research
|February 1, 2024
概括
拉尔蒂特雷克塞德 (RTX) 通过诱导细胞亡和内质网膜 (ER) 应激来抑制前列腺癌细胞的生长和迁移. 这种新的机制涉及降低热冲击蛋白家族A成员8 (HSPA8) 的调节,这表明RTX是潜在的前列腺癌治疗方法.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 前列腺癌,特别是抵抗割的前列腺癌 (CRPC),有效的治疗方法有限.
- CRPC转移是死亡的主要驱动因素.
- 在前列腺癌中Raltitrexed (RTX) 的治疗潜力尚未被探索.
研究的目的:
- 调查拉尔特雷克塞德 (RTX) 在治疗前列腺癌中的疗效.
- 阐明RTX在前列腺癌细胞中的作用的潜在分子机制.
- 评估RTX作为前列腺癌的潜在治疗剂.
主要方法:
- 细胞增殖,迁移,殖民地形成和亡测定是在DU145和PC-3前列腺癌细胞上进行的.
- 评估了反应性氧物种 (ROS) 的产生和内质网膜 (ER) 的压力.
- 研究了热冲击蛋白家族A成员8 (HSPA8) 的作用.
- 在体内有效性使用DU145异种移植小鼠模型进行了评估.
主要成果:
- RTX剂量取决于抑制前列腺癌细胞的增殖,迁移和殖民地形成,同时诱导亡.
- RTX增加了ROS生成,并激活了前列腺癌细胞中的ER压力信号.
- 发现HSPA8表达对RTX诱导的亡和ER压力至关重要;其通过RTX的下调被证实在体外和体内.
- 在异种移植模型中,RTX治疗减弱了瘤生长.
结论:
- RTX诱导前列腺癌细胞亡,并通过降低HSPA8的调节和激活ROS介导的ER压力来抑制瘤生长.
- RTX显示出作为前列腺癌治疗的新型治疗候选者的潜力.
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