在活体中,一种宏环-混合物的有效性可以选择性地调节β-catenin/TCF相互作用以抑制前列腺癌
Justine Habault1, Jennifer L Franco2, Susan Ha3
1Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA.
The Prostate
|February 16, 2025
概括
新的peptoid-peptide宏循环有效地准前列腺癌中的Wnt/β-catenin通路. 这种方法对治疗耐药性疾病的治疗有希望,抑制瘤生长和关键的瘤性途径.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 前列腺癌,虽然经常局部化和可治疗,但可以发展抵抗导致转移性割抵抗性前列腺癌 (mCRPC).
- Wnt/β-catenin通路涉及治疗耐药前列腺癌,使其成为治疗点.
- 针对β-catenin及其转录因子之间的相互作用是一个有希望的策略.
研究的目的:
- 评估类-类宏循环作为β-catenin/TCF相互作用的抑制剂.
- 在前列腺癌的临床前模型中评估这些宏循环的治疗潜力.
主要方法:
- 选一个peptoid-peptide宏循环库对β-catenin/TCF相互作用的选择性.
- 评估化合物 (MC13) 对它对β-catenin与E-cadherin结合的影响.
- 在前列腺癌小鼠异种移植和器官模型中测试MC13.
- 通过ChIP分析基因表达和蛋白质水平 (c-myc,axin2) 和β-catenin局部化.
主要成果:
- 宏循环选择性地针对β-catenin/TCF相互作用,而不会影响β-catenin/E-cadherin结合.
- 化合物MC13在体内表现出有效性,减少瘤生长和c-myc水平.
- 在前列腺癌有机体模型中,MC13抑制了生长,并降低了关键通路的调节,包括Wnt/β-catenin和c-myc.
- 染色体免疫沉证实了降低β-catenin与目标基因axin2和c-myc的结合.
结论:
- 类-类宏循环是β-catenin/TCF相互作用的有效抑制剂.
- MC13显示出治疗前列腺癌的治疗潜力,特别是耐药形式.
- 用宏循环准β-catenin是前列腺癌治疗的可行策略.
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