药理学抑制 Rho-kinase（ROCK）信号通路可增强神经母细胞瘤细胞对顺铂的耐药性。
Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells.
机构信息
Ghosh Science and Technology Center, Worcester State College, Worcester, MA 01602-2597, USA.
出版信息
Int J Oncol. 2010 Nov;37(5):1297-305. doi: 10.3892/ijo_00000781.
Abstract
The role of the RhoA/Rho kinase (ROCK) signaling pathway in cell survival remains a very controversial issue, with its activation being pro-apoptotic in many cell types and anti-apoptotic in others. To test if ROCK inhibition contributes to tumor cell survival or death following chemotherapy, we treated cisplatin damaged neuroblastoma cells with a pharmacological ROCK inhibitor (Y27632) or sham, and monitored cell survival, accumulation of a chemoresistant phenotype, and in vivo tumor formation. Additionally, we assayed if ROCK inhibition altered the expression of genes known to be involved in cisplatin resistance. Our studies indicate that ROCK inhibition results in increased cell survival, acquired chemoresistance, and enhanced tumor survival following cisplatin cytotoxicity, due in part to altered expression of cisplatin resistance genes. These findings suggest that ROCK inhibition in combination with cisplatin chemotherapy may lead to enhanced tumor chemoresistance in neuroblastoma.
摘要
RhoA/Rho 激酶（ROCK）信号通路在细胞存活中的作用仍然是一个非常有争议的问题，其在许多细胞类型中被激活具有促凋亡作用，而在其他细胞类型中则具有抗凋亡作用。为了测试 ROCK 抑制是否有助于化疗后肿瘤细胞的存活或死亡，我们用一种药理学 ROCK 抑制剂（Y27632）或假处理物处理顺铂损伤的神经母细胞瘤细胞，并监测细胞存活、获得耐药表型的积累以及体内肿瘤形成。此外，我们还检测了 ROCK 抑制是否改变了已知参与顺铂耐药的基因的表达。我们的研究表明，ROCK 抑制导致细胞存活增加、获得化疗耐药性，并增强顺铂细胞毒性后的肿瘤存活，部分原因是顺铂耐药基因表达的改变。这些发现表明，ROCK 抑制与顺铂化疗联合使用可能导致神经母细胞瘤的肿瘤化疗耐药性增强。
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