在临床前的模型中,布罗莫克里单一治疗克服了前列腺癌的化学抵抗
Lijuan Bai1, Xin Li2, Yang Yang3
1Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Molecular Oncology and Biomarkers Program, Georgia Cancer Center; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Translational oncology
|June 4, 2023
概括
勃罗莫克里因通过诱导细胞循环停止和亡来选择性地抑制耐化学性前列腺癌 (PCa) 细胞. 这种药物显示了临床前的疗效,这表明它可能用于治疗耐药PCa.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 化疗抵抗是治疗转移性割耐性前列腺癌 (PCa) 的一个重大挑战.
- 新型治疗策略对于改善化疗反应不良的患者的治疗结果至关重要.
研究的目的:
- 为了识别和评估抗化学性PCa细胞的新型抑制剂.
- 为了研究烯在PCa中的作用背后的分子机制.
主要方法:
- 表型查以确定候选药物.
- RNA测序 (RNA-seq) 用于分析基因表达变化.
- 西方涂抹以评估蛋白质表达.
- 在无体性裸体小鼠的体内异种移植研究.
主要成果:
- 甲酸被确定为抗化学性PCa细胞的强有力的抑制剂,诱导细胞循环停止和细胞亡.
- 通过RNA-seq检测发现,甲素会影响参与细胞循环调节,DNA修复和细胞死亡的基因,并与p53-p21-RB通路重叠.
- 布罗莫克里普丁增加了多巴胺D2受体 (DRD2) 表达和调节的信号通路 (AMPK,p38 MAPK,NF-κB,EZH2,生存).
- 勃罗莫克里单一治疗显著抑制了耐化学药PCa异种移植的瘤生长.
结论:
- 布罗莫克里普丁证明了临床前的有效性,作为抗化学药性PCa的选择性抑制剂.
- 其已确立的临床安全概况使其成为快速临床测试和重新使用的候选者.
- 勃罗莫克里普丁为克服前列腺癌化学抵抗提供了潜在的新治疗策略.
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