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狗前列腺癌细胞转录组显示PI3K/AKT/mTOR通路中的重要失调

Priscila E Kobayashi¹, Patrícia F Lainetti², Antonio F Leis-Filho¹

¹Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University, Botucatu, São Paulo, Brazil.

Journal of comparative pathology

|May 6, 2025

概括

拉帕米辛通过抑制mTOR显示了治疗狗前列腺癌的潜力. 然而,狗的前列腺癌细胞对拉帕素产生了耐药性,这凸显了对精准医学方法的需求.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
兽医医学兽医医学兽医医学

背景情况:

狗是独特的大型哺乳动物,与人类一起,自发地发展成前列腺癌.
狗前列腺癌的预后不好,治疗选择有限.
哺乳动物的拉帕素 (mTOR) 途径标在癌症发展中起着至关重要的作用.

研究的目的:

研究PI3K/AKT/mTOR通路在犬前列腺癌中的作用.
在狗前列腺癌模型中评估mTOR抑制剂Rapamycin的疗效.
在犬前列腺癌中识别对mTOR抑制的潜在抵抗机制.

主要方法:

对正常和癌症犬前列腺组织的基因表达微阵列分析.
生物信息丰富分析以确定激活的途径.
在实验室治疗狗前列腺癌细胞系 (PC1,PC2) 用不同度的拉巴素.
在治疗后评估细胞活力和基因表达 (AKT,mTOR,4E-BP1).

主要成果:

微阵列分析揭示了与PI3K/AKT/mTOR通路激活相关的显著差异性基因表达在狗前列腺癌中.
在癌细胞中观察到FKBP1A,FKBP1B,AKT1S1,PDK2,PIP5K1和PIP5KL1的表达增加.
拉巴胺治疗以剂量依赖的方式降低了细胞活力,但矛盾的是,增加了AKT转录水平,表明治疗耐药性.
拉帕米辛降低了mTOR和4E-BP1的表达,这表明部分途径受阻.

结论:

抑制mTOR是一种有前途的治疗策略,用于治疗狗前列腺癌.
获得对拉帕素的耐药性,特别是增加的AKT水平,是一个重大挑战.
需要进一步的研究和精准医学方法来克服狗前列腺癌的治疗耐药性.

关键词:

狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗全球基因表达全球基因表达在 mTOR 路径上.前列腺疾病前列腺疾病这种药物是拉帕米辛 (Rapamycin).

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