拉帕提尼布的抗瘤作用与PI3K和MAPK通路有关:对人类和狗前列腺癌细胞的分析
Carlos Eduardo Fonseca-Alves1,2, Antonio Fernando Leis-Filho1, Zara Alves Lacerda1
1Department of Veterinary Surgery and Animal Reproduction, São Paulo State University-UNESP, Botucatu-SP, Brazil.
PloS one
|April 2, 2024
概括
拉帕提尼布有效地抑制了人类前列腺癌 (PC) 细胞的迁移,并诱导了人类前列腺癌 (PC) 细胞的亡,但不是犬类PC细胞. 将拉帕提尼布与PI3K抑制剂结合使用可能会提高前列腺癌患者的治疗效率.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 异常的HER2激活驱动前列腺癌 (PC) 骨转移.
- 像拉帕提尼布这样的抗HER2疗法在PC中表现出不同的疗效.
- 在PC中报告了HER2过度表达,但治疗反应不一致.
研究的目的:
- 调查lapatinib在抑制细胞迁移和诱导人类和犬类PC细胞系中细胞亡方面的疗效.
- 为了分析对拉帕提尼布治疗反应的转录组变化.
- 识别潜在的耐药性机制和治疗策略.
主要方法:
- 用拉帕提尼布治疗人类 (LNCaP,PC3) 和犬类 (PC1,PC2) PC细胞系.
- 使用Annexin V/PI分析评估细胞迁移和细胞亡.
- 在拉帕提尼布治疗前后进行转录组分析.
主要成果:
- 拉帕提尼布增加了LNCaP细胞 (对雌激素敏感) 的亡和抑制迁移.
- 拉帕提尼布治疗后PC1,PC2和PC3细胞没有显著变化.
- 转录组分析显示了通路的丰富 (PI3K/AKT/mTOR在人体中,氨酸激酶/HER2在犬体中) 和MAPK在犬体细胞中的下调.
结论:
- 拉帕提尼布显示差异性疗效,有效于对雄激素敏感的人类PC细胞,但不适用于犬类或对雄激素不敏感的人类PC细胞.
- 狗PC的耐药性可能涉及MAPK下调;对雄激素不敏感的PC的耐药性可能涉及PI3K失调.
- 与拉帕蒂尼布和PI3K抑制剂的联合治疗可以增强PC患者的抗瘤反应和临床益处.
相关概念视频
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
01:19Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
02:34Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K